WO2012158613A1 - Pre-fusion rsv f antigens - Google Patents

Pre-fusion rsv f antigens Download PDF

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Publication number
WO2012158613A1
WO2012158613A1 PCT/US2012/037773 US2012037773W WO2012158613A1 WO 2012158613 A1 WO2012158613 A1 WO 2012158613A1 US 2012037773 W US2012037773 W US 2012037773W WO 2012158613 A1 WO2012158613 A1 WO 2012158613A1
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WO
WIPO (PCT)
Prior art keywords
fusion
rsv
atom
protein
polypeptide
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PCT/US2012/037773
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French (fr)
Inventor
Kurt Swanson
Andrea Carfi
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Novartis Ag
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Publication date
Priority to DK12722057.2T priority Critical patent/DK2707385T3/en
Priority to ES12722057.2T priority patent/ES2651143T3/en
Priority to RS20171155A priority patent/RS56748B1/en
Priority to MX2013013133A priority patent/MX351011B/en
Priority to CN201280034429.1A priority patent/CN103842374A/en
Priority to RU2013155485/10A priority patent/RU2013155485A/en
Priority to CA2835644A priority patent/CA2835644C/en
Priority to BR112013029169-9A priority patent/BR112013029169B1/en
Priority to EP12722057.2A priority patent/EP2707385B1/en
Priority to JP2014510534A priority patent/JP2014519819A/en
Priority to EP17191721.4A priority patent/EP3275892B1/en
Priority to PL17191721T priority patent/PL3275892T3/en
Priority to PL12722057T priority patent/PL2707385T3/en
Priority to SG2013081336A priority patent/SG194755A1/en
Application filed by Novartis Ag filed Critical Novartis Ag
Priority to LTEP12722057.2T priority patent/LT2707385T/en
Priority to US14/117,588 priority patent/US20140248314A1/en
Priority to SI201231135T priority patent/SI2707385T1/en
Priority to AU2012255971A priority patent/AU2012255971A1/en
Publication of WO2012158613A1 publication Critical patent/WO2012158613A1/en
Priority to US15/789,074 priority patent/US20180237476A1/en
Priority to HRP20171703TT priority patent/HRP20171703T1/en
Priority to CY20171101209T priority patent/CY1119849T1/en
Priority to CY20201100283T priority patent/CY1122826T1/en
Priority to US17/314,649 priority patent/US20210269489A1/en
Priority to US17/848,230 priority patent/US20220332766A1/en
Priority to US17/848,247 priority patent/US20220332767A1/en
Priority to US18/308,583 priority patent/US20230287056A1/en
Priority to FR23C1046C priority patent/FR23C1046I1/en
Priority to US18/596,426 priority patent/US20240239845A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • Respiratory syncytial virus is an enveloped non-segmented negative- strand RNA virus in the family Paramyxoviridae, genus Pneumovirus. It is the most common cause of bronchiolitis and pneumonia among children in their first year of life. RSV also causes repeated infections including severe lower respiratory tract disease, which may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems.
  • RSV conserved fusion protein
  • RSV F conserved fusion protein
  • the RSV F protein is translated from mRNA into an approximately 574 amino acid protein designated Fo.
  • Post-translational processing of Fo includes removal of an N- terminal signal peptide by a signal peptidase in the endoplasmic reticulum.
  • Fo is also cleaved at two sites (109/110 and 136/137) by cellular proteases (in particular furin) in the trans- Golgi. This cleavage results in the removal of a short intervening sequence and generates two subunits designated Fi (-50 kDa; C-terminal; approximately residues 137-574) and F 2 (-20 kDa; N- terminal; approximately residues 1-109) that remain associated with each other.
  • Fi contains a hydrophobic fusion peptide at its N-terminus and also two amphipathic heptad- repeat regions (HRA and HRB). HRA is near the fusion peptide and HRB is near the transmembrane domain. Three Fi-F 2 heterodimers are assembled as homotrimers of Fi-F 2 on the surface of the virion.
  • a vaccine against RSV infection is not currently available, but is desired.
  • Vaccine candidates based on the chief RSV neutralization antigen, the F glycoprotein have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the pre-fusion and post-fusion states. The magnitude of the rearrangement suggested that post-fusion F antigens would not efficiently elicit neutralizing antibodies, which presumably must bind epitopes exposed on the pre-fusion conformation. Accordingly, efforts to produce a vaccine against RSV have focused on developing subunit vaccines that contain pre-fusion forms of RSV F. (See, e.g., WO 2010/149745, WO 2010/149743, WO 2009/079796) This focus on pre-fusion forms of RSV F has been corroborated by available models of RSV F.
  • Pre-fusion F is a "metastable" structure that readily rearranges into the lower energy post-fusion state, which then aggregates due to exposure of a hydrophobic fusion peptide (Begona Ruiz-Arguello, M. et al. Virology 298, 317-326 (2002) (142)). Large structural differences between the lollipop-shaped pre-fusion F trimer and the crutch-shaped post- fusion F trimer are apparent even at the resolution of electron microscopy of negatively stained specimens, suggesting that pre-fusion and post-fusion F may be antigenically distinct (Calder, L. J. et al. Virology 271, 122-131 (2000) (143)).
  • the invention relates to pre-fusion respiratory syncytial virus (RSV) F polypeptides and pre-fusion chimeric F polypeptides.
  • RSV respiratory syncytial virus
  • the pre-fusion respiratory syncytial virus (RSV) F polypeptide comprises at least two introduced cysteine residues that are in close proximity to one another, and form a disulfide bond that stabilizes the pre-fusion RSV F polypeptide.
  • the HRB region contains an introduced cysteine residue and the DI and/or DII region contain an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residue in the HRB region and the introduced cysteine residue in the Dl or DII region.
  • the HRA region contains an introduced cysteine residue and the Dili region contains an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residue in the HRA region and the introduced cysteine residue in the III region. In other embodiments, the HRA region contains at least 2 introduced cysteine residues, and a disulfide bond is formed between the introduced cysteine residues in the HRA region.
  • the pre-fusion respiratory syncytial virus (RSV) F polypeptide comprises a post-fusion modification selected from the group consisting of deletion of the HRA helix, deletion of the HRB helix, introduction of point mutations, addition of glycosylation sites and combinations thereof, wherein said post-fusion modification destabilizes the post-fusion conformation.
  • the destabilizing post-fusion modification is deletion of the HRB helix, in whole or in part. If desired, the destabilizing post-fusion modification can further comprise deletion of the fusion peptide, in whole or in part.
  • the destabilizing post-fusion modification includes addition of a glycosylation site, such as glycosylation on a residue selected from the group consisting of position 173, position 175 and position 184.
  • the invention is a pre-fusion respiratory syncytial virus (RSV) F protein comprising three RSV F monomers, wherein at least two of the monomers contain an introduced cysteine residue, the introduced cysteine residues are in close proximity to one another and form a disulfide bond that stabilizes the pre-fusion RSV F protein.
  • RSV respiratory syncytial virus
  • the invention is a chimeric pre-fusion F protein comprising a stabilized F protein from a virus other than RSV, such as parainfluenza virus F polypeptide or a metapneumovirus virus F polypeptide, that contains one or more neutralizing epitope of RSV F.
  • a virus other than RSV such as parainfluenza virus F polypeptide or a metapneumovirus virus F polypeptide, that contains one or more neutralizing epitope of RSV F.
  • Suitable neutralizing epitopes can be selected from the group consisting of the epitopes that are recognized by motavizumab, palivizumab, mAb 11, mAb 151 , mAb 1129, mAb 1153, mAb 1200, mAb 1214, mAb 1237, mAb 47F, mAb 7C2, mAb B4, Fab 19, mAb AK13A2, mAb 7.936, mAb 9.936, mAb 19, mAb 20, mAb 101F and combinations thereof.
  • the invention relates to methods for inducing an anti -respiratory syncytial virus (RSV) immune response in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein.
  • RSV anti-respiratory syncytial virus
  • the induced immune response is characterized by neutralizing antibodies to RSV and/or protective immunity against RSV.
  • the invention relates to a method for inducing or raising neutralizing anti-respiratory syncytial virus (RSV) F protein antibodies in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein.
  • RSV anti-respiratory syncytial virus
  • the invention relates to a method for inducing or raising protective immunity against respiratory syncytial virus (RSV) in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein.
  • RSV respiratory syncytial virus
  • the invention relates to immunogenic compositions comprising a pre-fusion respiratory syncytial virus (RSV) F protein or a pre-fusion chimeric F protein.
  • RSV respiratory syncytial virus
  • the pre-fusion RSV F protein that is used in the invention can be full length or truncated, such as a soluble ectodomain that lacks the cytoplasmic and transmembrane domains.
  • the pre-fusion RSV F protein e.g., full length or soluble ectodomain, may comprise functional furin cleavage sites at positions 109/110 and 136/137.
  • that pre-fusion RSV F protein e.g., full length or soluble ecto-domain
  • the pre-fusion RSV F protein can be administered with or without an adjuvant as desired, and the immunogenic composition can comprise an adjuvant if desired.
  • FIG. 1 shows a structure-based sequence alignment of four F proteins, secondary assignment, and key features.
  • the alignment of RSV (SEQ ID NO:33), Newcastle disease virus (NDV) (SEQ ID NO:34), PIV3 (SEQ ID NO:36) and PIV5 (SEQ ID NO:35) Fs was generated with ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/), adjusted manually based on structural superposition using Lsqkab from the CCP4 suite of programs and displayed using ESPript version 2.2 (http://espript.ibcp.fr/ESPript ESPript ).
  • RSV F is indicated above the sequences; features of PIV3 F are indicated below the sequences.
  • *CHO indicates RSV F glycosylation sites.
  • Secondary structure elements are indicated, with arrows parallel to the sequences designating ⁇ -sheets, cylinders designating a- helices, "TT" designating turns, and coils designating 3 10 helices.
  • the domain location of secondary structure symbols are indicated (DI, DII, Dili), except for RSV helices ot5 and ot6, which are labeled to indicate that they form the Motavizumab binding site and ⁇ 20 and ⁇ 21, which are labeled to indicate that they form the 10 IF binding site.
  • Circled numbers (RSV) or triangled numbers (PIV3) designate residues that form disulfide bonds, with the same number for each partner in a disulfide-linked pair.
  • the furin cleavage sites for RSV F and PIV3 F are indicated by vertical arrows labeled Fr.
  • the RSV F p27 region released from the protein after furin cleavage is indicated by a black bar.
  • the fusion peptides of RSV F and PIV3 F are labeled.
  • the arrow in the fusion peptide indicates the first residue of the Fl fragment in the fusion peptide deletion construct used in this study.
  • Residues that are identical in all four proteins are indicated by shaded boxes.
  • Peptides used to investigate neutralizing binding sites are in open boxes and resistance mutations are indicated by asterisks.
  • FIG. 2 shows electron microscopy and circular dichroism analysis of the RSV F post- fusion trimer.
  • FIG. 2A an electron micrograph of the RSV F protein shows a field of uniform crutch phenotypes consistent with the structure of post-fusion F proteins.
  • FIG. 2B shows a CD melting curve of the post- fusion RSV F trimer observed at 210 nm, the observed spectral minimum of the folded RSV F protein. The CD absorption, y-axis, is plotted against temperature, x-axis.
  • FIG. 2C shows a CD spectra of the post-fusion RSV F trimer at 20° and 95°C. The spectra were recorded from 320 to 190 nm and show at both temperatures characteristic helical minima for a folded protein.
  • FIG. 3 shows representative electron densities of the crystallized RSV F protein.
  • FIG. 3A is a side view of the original molecular replacement solution model, which contains the PIV3 post- fusion head in- frame with the 6-helix bundle of RSV F, shown in the initial electron density map (1 ⁇ ) calculated after iterative real-space NCS three-fold averaging, histogram matching, and solvent flattening with phase extension from 7.0 to 3.2 A and no phase recombination. The head region fits poorly in the electron density.
  • FIG. 3B Side view. The final model of RSV F shown in the averaged electron density map as described in FIG. 4A.
  • FIG. 3C shows a top view of the RSV F protein structure shown in FIG. 4 A.
  • FIG. 3A is a side view of the original molecular replacement solution model, which contains the PIV3 post- fusion head in- frame with the 6-helix bundle of RSV F, shown in the initial electron density map (1 ⁇ ) calculated after iterative real-space NCS
  • FIG. 3D shows a top view of B. Model and electron density depicted as in FIG. 4B.
  • FIG. 3E is a close up of a representative averaged electron density (gray) with the final model in stick representation.
  • FIG. 3F shows the same view as in FIG. 4E but with final 2mFo-dFc electron density map contoured at 1.5 ⁇ .
  • FIG. 4 shows the RSV F ectodomain structure.
  • 4A is a linear diagram. Listed residue numbers correspond to the N-terminus of each segment, the furin cleavage sites (arrow heads), and the C-terminus. DI-III, domains I-III; p27, excised peptide; FP, fusion peptide; HRA, B, and C, heptad repeats A, B, and C.
  • 4B shows a ribbon representation of one subunit of the RSV F ectodomain trimer. Domains are labeled and shaded as in 4A, glycans are shown in black.
  • 4C shows surface representation of the RSV F ectodomain trimer. The domains of one subunit are labeled and shaded as in 4A, the other two subunits are white and gray.
  • FIG. 5 shows superposition of domains I and II of RSV F and PIV3 F.
  • FIG. 5A shows a ribbon diagram of domain I from RSV and PIV3 superimposed by matching the common ⁇ -sheets.
  • FIG 5B shows a ribbon diagram of domain II from RSV F and PIV3 F superimposed based on common ⁇ -strands. The secondary structure elements of RSV F are labeled.
  • FIG. 6 illustrates a comparison between RSV and PIV3.
  • FIG. 6 A is a ribbon diagram of RSV F domain III.
  • FIG. 6B shows a ribbon diagram of the PIV3 domain III oriented to match orientation shown in FIG. 6A.
  • FIG. 6C shows the detail of the RSV and PIV3 (which are shaded differently) domain III helical bundles superimposed based on domain III ⁇ -sheets.
  • FIG. 6D shows RSV and PIV3 F ectodomain trimers (shaded as in A and B) superimposed based on their six-helix bundles.
  • the image on the left shows a ribbon diagram viewed perpendicular to the three-fold axis; the image on the right is a surface representation viewed along the three-fold axis from the top of the head.
  • FIG. 7 illustrates the Motavizumab epitope.
  • FIG. 7A is a superposition of the Motavizumab-binding helices, ot5 and ot6, from the RSV F post-fusion trimer and the peptide-Motavizumab complex (PDB code 3 ⁇ ).
  • the post fusion trimer structure and the peptide-motavizumab complex structure are shaded differently.
  • RSV residues bound by Motavizumab are shown in stick representation. Asterisks denote Palivizumab escape mutations.
  • FIG. 7B shows a ribbon representation modeling a Motavizumab-RSV F post- fusion trimer complex.
  • VH and VL domains of the Fab are labeled; helices ot5 and ot6 from the RSV F structure and the peptide-Motavizumab structure are shaded differently; a glycan on RSV F is black; and the remainder of RSV F is white.
  • FIG. 8 illustrates RSV F conformational changes, antigenic structure and Palivizumab binding.
  • FIG. 8A is a surface representation of the post-fusion structure.
  • Antigenic sites A and C are outlined and labeled. Asterisks indicate residues selected in neutralization escape variants or forming contacts with an antibody in the determined structures of neutralizing antibody-peptide complexes.
  • the HRA and HRB surfaces are shaded.
  • FIG. 8B is a surface representation of a pre-fusion model, annotated as in A.
  • FIG. 8C is a graph showing inhibition of Palivizumab binding to post-fusion RSV F by pooled sera from un-immunized mice or mice immunized with the RSV F antigen. Palivizumab binding (percentage of ELISA signal without competing sera) is plotted as a function of the dilution of competing pooled sera.
  • FIG. 9 shows the exposure of the Motaviuzumab epitope in the post-fusion RSV F structure (A) and pre-fusion RSV F model (B).
  • Fig. 9A shows Domain III of one subunit from the post-fusion structure shaded black and grey while the remaining parts of RSV F are in white. Structural elements that do not significantly change betweeen pre- and post-fusion are in black while HRA (labeled with arrow), which refolds in the transition from the pre- to post-fusion conformation, is lighter grey.
  • Motavizumab epitopes on two subunits are also labeled.
  • a third Motavizumab epitope is present on the trimer surface, but is not easily visible in this orientation.
  • the Motavizumab epitope a5 and a6 helices are labeled on one example.
  • Fig. 9B shows Domain III of the pre-fusion model shaded as in A.
  • the fusion peptide region is shaded and labeled FP.
  • the HRA region is broken into structural elements al, a2, a3, ⁇ and ⁇ 2; labeled and shaded grey for one subunit.
  • the HRC loop may need to shift to accommodate antibody binding (as indicated by the arrow).
  • FIG. 10 shows a model of neutralizing antibody 101 F bound to the post- fusion RSV F trimer.
  • FIG. 10A shows the peptide (residues 431-435) (SEQ ID NO:37) from the 101F Fab-peptide complex structure (PDB code 3041 21 ) superposed on equivalent residues of the RSV F structure ( ⁇ -strand 20 to ⁇ -strand 21).
  • FIG. 10B is a ribbon representation of a model of the 101F Fab bound to the RSV F post-fusion trimer.
  • 101F Fab VH and VL domains are labeled; RSV F ⁇ -strand 20 and ⁇ -strand 21 and labeled as in A.
  • the remaining parts of RSV F are in white.
  • FIG. 10B discloses "IIKTF" as SEQ ID NO: 37.
  • FIGS. 11 A-C show that residues within appropriate distances to form disulfides can be identified, based on the current model of RSV F pre-fusion, can be identified.
  • FIG. 11A Center
  • the pre-fusion RSV F model is shaded/colored to show structural features which are labeled ( HRB, HRA, Dili).
  • FIG. 11B (Left) is a zoom-in view of the packing of HRA on domain III in the pre-fusion model.
  • the paired numbers indicate residues in close proximity which, if mutated to cysteines could form a disulfide bond.
  • FIG. l lC (Right) is a zoom-in view of the packing of the HRB -stalk on domains I and III (white).
  • paired numbers indicate residues which, if mutated to cysteines could form a disulfide bond.
  • Amino acid residues 165 and 296, and 56 and 164 are not at ideal distances to one another, in the pre-fusion model, to form disulfide bonds, but are in correct orientation and can form disulfides if the model is biased by the PIV5 structure, on which the model was built.
  • FIG. 12 shows a negative stained electron micrograph of the HRB-deleted RSV F construct (RSV F delHRB HIS, SEQ ID NO:28). Electron microscopy of the HRB- deleted RSV F construct demonstrated the RSV F protein formed rosettes, likely through the fusion peptide. The formation of rosettes through the fusion peptide is a feature of post- fusion RSV F rather than a predicted behavior of pre-fusion F proteins (Ruiz-Arguello et al. 2004 (142) and Connolly et al, 2006 (144)). This result shows the HRB-deleted RSV F construct does not appreciably stabilize the protein in the desired pre-fusion conformation.
  • FIG. 13 shows the structure of RSV F protein in which certain mutations are introduced to inhibit 6-helix bundle formation. Shown is the RSV F post-fusion structure in which the HRB helix has been removed and replaced with a hypothetical random coil (represented by the lines). The elongated HRA helix of the post-fusion RSV F is labeled. The numbers represent potential sites for introduced glycosylation sites or other mutations which interfere with formation of the 6-helix bundle characteristic of the post-fusion structure. A mutation on the HRA helix which interferes with HRB interaction would destabilize the post- fusion conformation, which in turn would cause the protein to remain in the favored pre- fusion conformation.
  • FIGs. 14 A and B are western blots of cell lysates (14A, showing total expression) or media (14B, showing secreted protein) under boiled and reducing conditions using an anti-His tag antibody.
  • the westerns show the expression of RSV-F proteins, and that proteins with engineered cysteine residues were expressed and contained intra-chain disulfide bonds. Cleavage of RSV F protein from F0 to F1/F2 and secretion from the cell is evidence of proper protein folding of the RSV F proteins. Migrations for uncleaved F0 and cleaved Fl are indicated. The key for gel lane labeling is shown above the blots.
  • R049 RSV-F fus del R429S I432T K433T S436F trunc (SEQ ID NO:39); R050: RSV-F HRA Disulfide2 I57C S190C trun (SEQ ID NO:40); R051 : RSV-F HRA Disulfide3 T58C V164C trunc (SEQ ID NO:6); R052: RSV-F HRA Disulfide5 K168C V296C trunc (SEQ ID NO:8); R053: RSV- F fus del N262Y N268I K272M R429S I432T K433T S436F trunc (SEQ ID NO:41); R054 RSV-F HRA Disulfidel V56C V164C trunc (SEQ ID NO:4); R055 RSV-F HRA Disulfide4 N165C V296C trunc (SEQ ID NO:
  • FIGs. 15 A - C show SEC analysis of RSV F intra-chain disulfide. Postfusion F rosettes and fusion peptide deleted RSV F trimers were used to develop an HPLC-SEC assay to differentiate between rosettes and trimers.
  • FIG. 15 A Fusion peptide- stabilized RSV F rosettes migrated with the void volume by SEC (retention time of 5 minutes on Bio- Sil 250 SEC column). Anti-HIS-tag western blotting confirmed that the protein was in the void volume peak.
  • FIG. 15 B Fusion peptide-deletion RSV F trimers migrated with an SEC retention time of approximately 6.5 minutes. Anti-HIS-tag western blot similarly confirmed that the protein was in the included volume trimer peak.
  • FIGs. 16 A - C show purification and analysis of RSV F protein constructs that contain engineered cysteins.
  • FIG 16 A shows purification of the RSV F N165C/V296C construct. Columns are labeled for flow-through (FT), wash (W), elution (E) and resin (R) from a chelating purification. Unlike other protein constructs that contained introduced disulfide mutations and were expressed in insect cells, N165C/V296C secreted as a cleaved species, similar to its profile when expressed in mammalian cells.
  • FIG. 16 B shows a gel- shift analysis of the K168C/V296C and M396C/F483C RSV F protein constructs.
  • the two constructs run with boiling and reducing agent present.
  • the two constructs are run after boiling with no reducing agent (b/nr) or no boiling and no reducing agent (nb/nr).
  • the western blot shows the protein is largely uncleaved, but that unexpectedly no inter-chain disulfide bonds were formed.
  • FIG. 16 C shows a coomasie-stained gel of the K168C/V296C and M396C/F483C RSV F protein constructs with reducing and boiling. Approximately 50% of the material was cleaved.
  • FIG. 17(A) shows electron microscopy analysis of NDV F (prefusion) with the expected spherical heads for prefusion F, with a few rosette-like aggregates.
  • FIG. 17(B) shows NDV prefusion F forms rod-like crystals. An isolated rod was analyzed and a dataset with -95% completion to -3.7 angstroms was recorded.
  • FIG, 17 (C) shows NDV prefusion F forms bipiramidal crystals (50x50x50 ⁇ size).
  • FIGs. 18 A-E show analysis of several RSV F protein constructs.
  • FIG. 18A shows EM analysis of RSV F Del-HRB showing that 100% formed rosettes. The protein eluted from the SEC column in the void/rosette retention peak.
  • FIG. 18(B) shows analysis/purification of the Del-HRB Del-FP RSV F construct. The protein was found in both the void and trimer retention peaks.
  • FIG. 18C shows gel-analysis, which suggests that there was partially cleaved RSV F Del-HRB Del-FP present in both the void and trimer peaks.
  • FIG. 18D shows EM of NDV F (prefusion), which shows the expected spherical heads for pre-fusion F with a few rosette-like aggregates.
  • FIG. 18E shows that RSV F Del- HRB from the SEC trimer peak contains a heterogeneous mix of rosette-like structures, post- fusion crutches and pre-fusion head-like spherical species.
  • FIG. 19 shows SDS-PAGE analysis of chimeric RSV F/NDV and RSV F/PIV5 F protein constructs.
  • the supernatant from cells transfected with one of the six constructs (1 : RSV-F NDV HRB del fus trunc; 2: RSV-F NDV HRB trunc; 3: RSV-F NDV HRB2 del fus trunc; 4: RSV-F NDV HRB2 trunc; 5: RSV-F PIV5 HRB del fus trunc; 6: RSV-F PIV5 HRB trunc) was analyzed by SDS-PAGE.
  • the constructs were engineered with or without (del fus) fusion peptide.
  • the proteins either had an NDV HRB, an NDV HRB with an additional glycine residue as a linker (HRB2) or PIV5 HRB as indicated.
  • HRB2 an NDV HRB with an additional glycine residue as a linker
  • PIV5 HRB an additional glycine residue as a linker
  • pre-fusion RSV F proteins are RSV F proteins that share general structural architecture more similar to the PIV5 pre-fusion structure rather than the RSV F post-fusion structure.
  • Pre-fusion RSV F proteins include the following
  • the HRA region is packed against domain III in the RSV F head region and/or the HRB region forms a trimer coil-coil stalk in proximity to domains I and II rather than associating with the HRA region in the context of the 6-helix bundle.
  • post- fusion conformation of RSV F protein are RSV F proteins that share more general structural architecture with the RSV F post-fusion structure rather than the PIV5 pre-fusion structure.
  • Post- fusion RSV F proteins include an HRA-HRB 6-helix bundle.
  • HRA region in prefusion RSV F is approximately residues 137-239 of RSV F protein (SEQ ID NOS: 1 and 2) and comprises the fusion peptide, helix Oil , helix ot2, helix ot3, helix ot4, strand ⁇ ⁇ and strand ⁇ 2. See, FIG. 9B.
  • the HRA helix in post fusion RSV F is formed by approximately residues 155-226 of RSV F protein (SEQ ID NOS: 1 and 2).
  • the fusion peptide is defined by residues 137-154 of RSV F protein (SEQ ID NOS: 1 and 2).
  • helix Oil in the prefusion RSV F HRA region is formed by approximately residues 145-157 of RSV F protein (SEQ ID NOS: 1 and 2).
  • helix ot2 in the prefusion RSV F HRA region is formed by approximately residues 158-167 of RSV F protein (SEQ ID NOS: 1 and 2).
  • helix ot3 in the prefusion RSV F HRA region is formed by approximately residues 168-176 of RSV F protein (SEQ ID NOS: 1 and 2).
  • helix ot4 in the prefusion RSV F HRA region is formed by approximately residues 194-212 of RSV F protein (SEQ ID NOS: 1 and 2).
  • strand ⁇ in the prefusion RSV F HRA region is formed by approximately residues 177-184 of RSV F protein (SEQ ID NOS: 1 and 2).
  • strand ⁇ 2 in the prefusion RSV F HRA region is formed by approximately residues 185-193 of RSV F protein (SEQ ID NOS: 1 and 2).
  • HRB region in RSV F is approximately residues 461-515 of RSV F protein (SEQ ID NOS: 1 and 2) and includes the HRB helix and the HRB linker [049] As used herein, the HRB helix in RSV F is formed by approximately residues 485-515 of RSV F protein (SEQ ID NOS: 1 and 2).
  • the HRB linker in RSV F is formed by approximately residues 461 - 484 of RSV F protein (SEQ ID NOS: 1 and 2).
  • domain I is formed by approximately residues 26 - 50 and 309 - 401 of RSV F protein (SEQ ID NOS: 1 and 2).
  • domain II is formed by approximately residues 400 - 460 of RSV F protein (SEQ ID NOS: 1 and 2).
  • domain III is formed by approximately residues 51 -98 and 206 - 308, or residues 51 - 308 of RSV F protein (SEQ ID NOS: 1 and 2).
  • a purified protein or polypeptide is a protein or polypeptide which is recombinantly or synthetically produced, or produced by its natural host, and has been isolated from other components of the recombinant or synthetic production system or natural host such that the amount of the protein relative to other macromolecular components present in a composition is substantially higher than that present in a crude preparation.
  • a purified protein will be at least about 50% homogeneous and more preferably at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95% or substantially homogeneous.
  • substantially free of lipids and lipoproteins refers to compositions, proteins and polypeptides that are at least about 95% free of lipids and lipoproteins on a mass basis when protein and/or polypeptide (e.g., RSV F polypeptide) purity is observed on an SDS PAGE gel and total protein content is measured using either UV280 absorption or BCA analysis, and lipid and lipoprotein content is determined using the Phospholipase C assay (Wako, code no. 433-36201).
  • polypeptide e.g., RSV F polypeptide
  • close proximity refers to a distance of not more than about 10A, not more than about 8 A, not more than about 6A, not more than about 4A, or not more than about 2A.
  • the distance between the alpha carbons of the amino acid residues are is more than about 10A, not more than about 8A, not more than about 6A, not more than about 4A, or not more than about 2A.
  • RSV F protein suitable for use in this invention are described herein with reference to particular amino acids that are identified by the position of the amino acid in the sequence of RSV F protein from the A2 strain (SEQ ID NO: 1).
  • RSV F proteins can have the amino acid sequence of the F protein from the A2 strain or any other desired strain.
  • the amino acids of the F protein are to be numbered with reference to the numbering of the F protein from the A2 strain, with the insertion of gaps as needed. This can be achieved by aligning the sequence of any desired RSV F protein with the F protein of the strain A2. Sequence alignments are preferably produced using the algorithm disclosed by Corpet, Nucleic Acids Research, 1998, 16(22): 10881-10890, using default parameters (Blossum 62 symbol comparison table, gap open penalty: 12, gap extension penalty: 2).
  • the 3.2 A x-ray crystal structure of a post- fusion form of RSV F protein has been determined.
  • a model of the pre-fusion form of RSV F protein was made by comparing the RSV F post-fusion x-ray crystal structure to the known structures of the pre- and post-fusion parainfluenza virus F proteins.
  • This model of the pre-fusion form of RSV F reveals structural features that differ from those of prior models of pre-fusion RSV F and allows for rational structure-based design of stabilized pre-fusion forms of RSV F.
  • the invention relates to pre-fusion respiratory syncytial virus F (RSV F) polypeptides and/or proteins, and immunogenic compositions comprising pre-fusion RSV F polypeptides and/or proteins.
  • RSV F respiratory syncytial virus F
  • the invention also relates to methods and use of pre- fusion RSV F polypeptides and/or proteins for inducing an immune response, and or by protective immunity against RSV.
  • the invention also relates to nucleic acids that encode pre-fusion RSV F polypeptides and/or proteins.
  • the immunogenic compositions comprise pre-fusion RSV F polypeptides and/or proteins that elicit neutralizing antibodies.
  • Pre-fusion and post-fusion PIV F structures reveal en bloc shifts of domains and large rearrangements of HRA and HRB.
  • HRA folds into three a-helices and two ⁇ -strands rather than the long post-fusion HRA helix (Yin et al, 2006).
  • the non-rearranging parts superimpose well.
  • Superimposing post- fusion RSV F domains on their pre-fusion PIV5 F counterparts did not result in major clashes and positioned all the pairs of cysteines that form interdomain disulfide bonds in proximity to each other.
  • the pre-fusion RSV F model obtained by thus combining information from the post- fusion RSV F x-ray crystal structure and the pre-fusion PIV5 F structure revealed a feature not apparent from prior homology models of pre-fusion RSV F based solely on the PIV5 pre-fusion structure (McLellan et al NSMB 2010 (141)).
  • the helices of the Palivizumab/Motivizumab epitope are exposed on the surface of the pre-fusion RSV F trimer model, as they are on post-fusion RSV F trimer x-ray crystal structure ( Figure 9).
  • the pre-fusion model disclosed herein which is based on the RSV F post- fusion x-ray crystal structure and the PIV5 prefusion structure (Yin et al, 2006 (145)), shows that the elongated HRA helix of the post-fusion RSV F (residues 137-212) folds into strands and helices similar to the PIV5 pre-fusion crystal structure.
  • the fusion peptide of RSV F, residues 137-154, forms a coil and helix that is packed into the RSV F pre-fusion head.
  • helix al is approximately residues 145-157
  • helix a2 is approximately residues 158-167
  • helix a3 is approximately residues 168-176
  • helix a4 is approximately residues 194-212.
  • Two strands are formed; strand bl is approximately residues 177-184, strand b2 is approximately residues 185-193 ( Figure 9).
  • the invention includes pre-fusion RSV F polypeptides and proteins and immunogenic compositions that contain pre-fusion RSV F polypeptides and proteins.
  • the RSV F protein and polypeptides can contain 1 or more amino acid replacements, deletions and/or additions that stabilize the pre-fusion conformation or destabilize the post-fusion conformation, for example, a pre-fusion RSV F stabilized with disulfide bonds, or a prefusion RSV F formed by destabilizing the post- fusion conformation.
  • the RSV F pre-fusion model may be used as a guide to select amino acid residues that are in close proximity to each other in the pre-fusion conformation and that are no longer in close proximity in the post-fusion conformation.
  • amino acids may be mutated to cysteine residues to allow disulfide formation that stabilizes the prefusion conformation, for example by preventing the HRB helix from associating with the HRA helix, thus preventing refolding to the post-fusion conformation.
  • a stabilized pre-fusion RSV F protein of the invention may comprise a disulfide bond between any two structural elements, or between one structural element and the remainder of the RSV F protein, or between a structural element of one subunit of a trimer and a structural element of another subunit of the same trimer.
  • a first amino acid in one structural element and a second amino acid that is in a different structural element, or the same structural element on a separate monomer, and that is also in close proximity to the first amino acid in the prefusion model are selected for replacement with cysteine.
  • the distance between the residues can be less than about 10A, less than about 8A, less than about 6A, less than about 5 A, less than about 4A, or less than about 3A.
  • the cysteine replacements of the first amino acid and the second amino acid, and a disulfide bond between them can be modeled.
  • the length of the modeled disulfide bond in some embodiments, does not exactly match the ⁇ 2A length considered to be optimal for disulfide bonds.
  • the modeled disulfide bond length (distance between sulfur nuclei) is about 0.5A-3.5A, about 1.0A-3.0A, or about 1.5A-2.5A, which, due to structural flexibility, are expected to form disulfide bonds in the protein.
  • pre-fusion RSV F protein may be stabilized in the prefusion conformation through the introduction of at least one cysteine mutation in a first structural element in close proximity to at least one other cysteine (natural or introduced) in a second structural element or the remaining RSV F head region. Disulfide bonds form between the introduced cysteine that prevent the post- fusion HRA-HRB six-helix bundle from forming.
  • pre-fusion RSV F protein may be stabilized in the pre-fusion conformation through the introduction of at least one cysteine mutation in the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2, DI, DII, or Dili in close proximity to at least one other cysteine (natural or introduced) in a different structural region (e.g., selected from the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2, DI, DII, or Dili), thereby forming one or more disulfide bridges that would prevent the post- fusion HRA-HRB six -helix bundle from forming.
  • a different structural region e.g., selected from the HRA helix region, HRB helix region
  • the cysteines may be introduced to the HRB or the HRB linker to create disulfide bonds between the cysteines.
  • one or more cysteines may be introduced to the HRB linker and helix region (approximately residues 452 to 515) to form disulfides with portions of the RSV F head region.
  • a disulfide bond between the HRB linker or helix and the remainder of the RSV F protein may be used to stabilize the protein in the pre-fusion conformation.
  • a disulfide bridge is formed between the HRB pre-fusion stalk and the DI or DII region at the "top" of the head (e.g., M396C + F483C).
  • the pre-fusion RSV F protein comprises two cysteine mutations, M396C and F483C, thereby comprising a disulfide bond between the HRB pre-fusion stalk and the DI region.
  • a disulfide bridge is formed between the HRA region and Dili region.
  • the RSV F protein can contain amino acid
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the HRA region, and a second cysteine (natural or introduced) in the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2 of the pre-fusion HRA region, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the HRB helix region, and a second cysteine (natural or introduced) in DI or DII.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six -helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the fusion peptide, and a second cysteine (natural or introduced) in the HRA region, helix al, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2 or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA elongated helix from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the helix al, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a2, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al , helix a3, helix a4, strand ⁇ , strand ⁇ 2, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a3, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al , helix a2, helix a4, strand ⁇ , strand ⁇ 2, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a4, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al, helix a2, helix a3, strand ⁇ , strand ⁇ 2, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the strand ⁇ , and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ 2, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the strand ⁇ 2, and a cysteine (natural or introduced) in the HRA helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ , DI, DII, or Dili.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the DI region, and a second cysteine (natural or introduced) in the HRB helix region.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the DII region, and a second cysteine (natural or introduced) in the HRB helix region.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first cysteine mutation in the Dili region, and a second cysteine (natural or introduced) in the HRA helix region.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
  • the pre-fusion RSV F protein comprises a first introduced cysteine in the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand ⁇ , strand ⁇ 2, DI, DII, or Dili region and a second cysteine (natural or introduced) in any other region of the RSV F protein that is in close proximity to the introduced cysteine.
  • the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six -helix bundle from forming.
  • the pre-fusion RSV F protein comprises two cysteine mutations selected from the group consisting of V56C + V164C, I57C + S190C, T58C+V164C, N165C+V296C, and K168C + V296C, and combinations thereof, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, V56C and V164C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, I57C and S190C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, T58C and V164C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, N165C and T296C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, K168C and T296C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
  • the pre-fusion RSV F protein comprises two cysteine mutations, M396C + F483C, thereby comprising a disulfide bridge between the HRB region and the DII region.
  • the RSV F pre-fusion protein of the present invention is stabilized in the pre- fusion conformation by mutations that stabilize the pre-fusion subunit, which forms trimers.
  • the RSV F pre-fusion protein of the present invention is a trimer of RSV F monomers, and pre-fusion conformation is stabilized by one or more disulfide bonds between cysteine residues that are introduced into different monomers.
  • the pre-fusion RSV F protein of the invention can contain any of the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
  • a major feature of the RSV F post-fusion structure is the 6-helix bundle in the stalk region.
  • the three HRA helices and the three HRB helices form a very stable 6-helix bundle.
  • An alternative strategy for producing a stabilized pre-fusion RSV F protein of the invention is by destabilizing the post-fusion 6-helix bundle, and/or preventing the 6-helix bundle formation (e.g., through deletion of the HRB helix, introduction of point mutations, addition of glycosylation or other modification sites).
  • the 6-helix bundle formation may be prevented by deleting the HRA helix or the HRB helix.
  • the HRB helical region is deleted or mutated to prevent formation of the post-fusion conformation.
  • the HRB region forms the stalk of the RSV F pre-fusion conformation, is in close proximity to the viral membrane and likely does not contain
  • a stabilized pre-fusion RSV F protein of the invention may comprise the RSV ectodomain sequence with the HRB region deleted or mutated, and preferably further
  • the RSV ectodomain may comprise one or more introduced cysteines to create disulfide bridges that stabilize the prefusion structure as described herein, mutated or deleted furin cleavage sites, mutated or deleted fusion peptide sequence, or other mutations previously described in WO 2011/008974, incorporated herein in its entirety.
  • the RSV ectodomain may be the ectodomain of a naturally occurring RSV F protein, or it may contain mutations in addition to the deletions and/or mutations of the HRA or HRB region.
  • the stabilized pre-fusion RSV F protein comprises an ectodomain of a naturally occurring RSV F protein in which the HRB region is deleted and one or more mutations that prevent cleavage at one or both of the furin cleavage sites (i.e, amino acids 109 and 136 of SEQ ID NOS: l and 2) are present.
  • the stabilized pre-fusion RSV F protein comprises an ectodomain of a naturally occurring RSV F protein in which the HRB region is deleted and the fusion peptide is mutated (amino acids 137 and 153 of SEQ ID NOS: 1 or 2).
  • this region can be deleted in whole or in part.
  • the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region and the fusion peptide is deleted, in whole or in part.
  • the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and an oligomerization sequence has been added.
  • an oligomerization sequence is present, it is preferably a trimerization sequence.
  • Suitable oligomerization sequences are well known in the art and include, for example, the coiled coil of the yeast GCN4 leucine zipper protein, trimerizing sequence from bacteriophage T4 fibritin ("foldon”), and the trimer domain of influenza HA.
  • the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and the p27 region is mutated (amino acids 110-136 of SEQ ID NOS: 1 or 2), including deletion of the p27 region in whole or in part.
  • lysine and/or arginine residues in the p27 region can be substituted or deleted.
  • the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and an amino acid sequence that provides a protease cleavage site is added.
  • the amino acid sequence that provides a protease cleavage site will be located within about 60 amino acids, about 50 amino acids, about 40 amino acids, about 30 amino acids, about 20 amino acids, about 10 amino acids, or substantially adjacent to the amino terminus of the transmembrane domain (amino acid 525 of SEQ ID NO: l or 2).
  • the pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
  • the stabilized pre-fusion RSV F protein of the invention may also be formed by hindering 6-helix bundle formation in the HRA or HRB regions (approximately residues 154-212 and 484 to 513, respectively) through engineered point mutations or introduction of glycosylation sites (e.g., AsnXaaSer/Thr; SEQ ID NO:l 1) or other modification sites (e.g., lipidation, phosphorylation).
  • glycosylation sites e.g., AsnXaaSer/Thr; SEQ ID NO:l 1
  • Glycosylation sites, or other post-translational modification sites or point mutations which interfere with 6-helix bundle formation through electrostatic or steric hindrance, can be introduced through the HRA or HRB helical regions. Glycosylation can interfere with 6-helix bundle formation and prevent flipping of the RSV F construct to the post-fusion conformation.
  • a stabilized pre-fusion RSV F protein of the invention may comprise one or more mutations that form one or more glycosylation sites in the HRA or HRB helical regions.
  • the RSV F protein may contain mutations or deletions in addition to those that introduce the glycosylation sites in the HRA or HRB helical regions.
  • the RSV F protein comprises S173N and N175T mutations and the pre-fusion RSV F protein has a glycosylation site on current serine residue 173.
  • the RSV F protein comprises a mutation A177T, so that the pre-fusion RSV F protein has a glycosylation site on current residue N175.
  • the RSV F protein comprises G184N and S186T mutations and the pre-fusion RSV F protein has a glycosylation site on current residue G184. Chimeric pre-fusion F structures with relevant RSV F epitopes
  • the invention also relates to chimeric pre-fusion F proteins that contain neutralizing epitopes from RSV F protein.
  • the chimeric pre-fusion F proteins comprise a stabilized F protein from a different virus, such as the Parainfluenza Virus (PIV1, PIV2, PIV3, PIV4, PIV5), Newcastle Disease Virus (NDV), Sendai virus (SeV), Hendra Virus, Nipah Virus (NiV), human metapneumovirus or avian metapneumovirus, in which portions that are exposed on the surface of the protein are replaced with corresponding portions of RSV F.
  • the portions contain neutralizing epitopes of RSV F.
  • any non-RSV (e.g., parainfluenza virus or metapneumovirus) F protein that is stabilized in the pre-fusion conformation may be used as a template for the protein (i.e., an uncleaved NDV F-GCN fusion protein).
  • the SV5 of PIV5 pre-fusion F protein described by Yin et al., 2006 (145) or the NDV pre-fusion F described by Swanson et al, 2010 (146) may be used in the chimeric F protein construct.
  • the template may then be mutated to introduce known or suspected neutralizing epitopes of RSV F.
  • the protein may have a pre-fusion F structure exhibiting the neutralizing epitopes, but not non- neutralizing epitopes, of RSV F.
  • a clear benefit to this construct is that it would not raise non-neutralizing RSV F antibodies.
  • a pre-fusion chimera protein of the invention may comprise a parainfluenza virus F protein, stabilized in the pre-fusion conformation that is mutated to introduce neutralizing epitopes of RSV F.
  • the parainfluenza virus F protein may be any parainfluenza virus F protein, preferably the SV5 of PIV5 pre-fusion F protein, described by Yin et al., 2006 (147) or the NDV pre-fusion F described by Swanson et al, 2010 (146).
  • Exemplary neutralizing epitopes that may be introduced by mutation include the epitopes disclosed in Table 1.
  • the amino acids that form the epitopes recognized by the antibodies listed in Table 1 can be introduced into the corresponding positions (e.g., identified by structural comparison, such as structure based alignment) of a non RSV-F protein (e.g., parainfluenza virus F protein or metapneumovirus F protein) that is stabilized in the pre- fusion conformation.
  • a non RSV-F protein e.g., parainfluenza virus F protein or metapneumovirus F protein
  • the chimeric F protein can contain the RSV F site A epitope or site C epitope.
  • the chimeric F protein contains one or more RSV F residues selected from the amino acid residues at positions 262 - 276 of RSV F.
  • the chimeric F protein contains one or more RSV F residues selected from the amino acid residues at positions 429 - 447 of RSV F.
  • An escape mutation is included if it is the sole mutation in an antibody-resistant strain.
  • d Fabl9 and 19 are unrelated antibodies. The similar names are coincidental.
  • the chimeric F protein of the invention comprises the HRA region of RSV F (residues 137-212) in place of the equivalent HRA residues of NDV- GCN pre-fusion F.
  • prefusion F protein NDV-GCN
  • potential neutralizing epitope sites HRA region of RSV F
  • Additional neutralizing epitopes may be added if desired, for example the motavizumab epitope or the 10 IF epitope.
  • the presented sequences contain a signal peptide, a GCN-trimerization domain and a HIS tag.
  • the chimeric pre-fusion F protein of the invention can contain the amino acid sequence shown below, with or without the signal peptide and/or GCN-trimerization domain and/or HIS tag.
  • RSV HRA prefusion underlined portion is RSV HRA, italicized portion is C-terminal GCN trimeric domain and HIS6 (SEQ ID NO: 12) affinity purification tag) (SEQ ID NO: 13).
  • the F glycoprotein of RSV directs viral penetration by fusion between the virion envelope and the host cell plasma membrane. It is a type I single-pass integral
  • SS N-terminal ER-translocating signal sequence
  • ED ectodomain
  • TM transmembrane domain
  • CT cytoplasmic tail
  • the F protein in RSV can mediate entry and syncytium formation
  • the hRSV F mRNA is translated into a 574 amino acid precursor protein
  • F 0 which contains a signal peptide sequence at the N-terminus that is removed by a signal peptidase in the endoplasmic reticulum.
  • Fo is cleaved at two sites (a.a. 109/110 and 136/137) by cellular proteases (in particular furin) in the trans-Golgi, removing a short
  • Fi contains a hydrophobic fusion peptide at its N-terminus and also two hydrophobic heptad-repeat regions (HRA and HRB). HRA is near the fusion peptide and HRB is near to the transmembrane domain (See, e.g. , FIG. 4A).
  • the Fi-F 2 heterodimers are assembled as homotrimers in the virion.
  • RSV exists as a single serotype but has two antigenic subgroups: A and B.
  • the F glycoproteins of the two groups are about 90% identical.
  • the A subgroup, the B subgroup, or a combination or hybrid of both can be used in the invention.
  • An example sequence for the A subgroup is SEQ ID NO: 1 (A2 strain; GenBank GI: 138251 ; Swiss Prot P03420), and for the B subgroup is SEQ ID NO: 2 (18537 strain; GI: 138250; Swiss Prot P13843).
  • SEQ ID NO: l and SEQ ID NO:2 are both 574 amino acid sequences.
  • the signal peptide in A2 strain is a.a. 1-21, but in 18537 strain it is 1-22.
  • the TM domain is from about a.a. 530-550, but has alternatively been reported as 525-548.
  • the invention may use any desired RSV F amino acid sequence, such as the amino acid sequence of SEQ ID NO: 1 or 2, or a sequence having identity to SEQ ID NO: 1 or 2. Typically it will have at least 75% identity to SEQ ID NO: 1 or 2 e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%,identity to SEQ ID NO: l or 2. The sequence may be found naturally in RSV.
  • an ectodomain of F protein in whole or in part, it may comprise:
  • polypeptide comprising an amino acid sequence having at least 75% identity (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% identity) to (i) or (ii).
  • a polypeptide comprising a fragment of (i), (ii) or (iii), wherein the fragment comprises at least one F protein epitope.
  • the fragment will usually be at least about 100 amino acids long, e.g. , at least about 150, at least about 200, at least about 250, at least about 300, at least about 350, at least about 400, at least about 450 amino acids long.
  • the ectodomain can be an Fo form with or without the signal peptide, or can comprise two separate peptide chains (e.g., an Fi subunit and a F 2 subunit) that are associated with each other, for example, the subunits may be linked by a disulfide bridge. Accordingly, all or a portion of about amino acid 101 to about 161, such as amino acids 110-136, may be absent from the ectodomain.
  • the ectodomain in whole or in part, can comprise:
  • a first peptide chain and a second peptide chain that is associated with the first polypeptide chain where the first peptide chain comprises an amino acid sequence having at least 75% identity (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or even 100% identity) to about amino acid 22 to about amino acid 101 of SEQ ID NO: 1 or to about amino acid 23 to about amino acid 101 of SEQ ID NO: 2, and the second peptide chain comprises an amino acid sequence having at least 75% identity (e.g.
  • first peptide chain and a second peptide chain that is associated with the first polypeptide chain
  • first peptide chain comprises an amino acid sequence comprising a fragment of about amino acid 22 to about amino acid 101 of SEQ ID NO: 1 or of about amino acid 23 to about amino acid 109 of SEQ ID NO: 2
  • second peptide chain comprises a fragment of about amino acid 162 to about amino acid 525 of SEQ ID NO: 1 or of about amino acid 161 to about amino acid 525 of SEQ ID NO: 2.
  • One or both of the fragments will comprise at least one F protein epitope.
  • the fragment in the first peptide chain will usually be at least 20 amino acids long, e.g.
  • the fragment in the second peptide chain will usually be at least 100 amino acids long, e.g. , at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450 amino acids long.
  • an amino acid sequence used with the invention may be found naturally within RSV F protein (e.g., a soluble RSV F protein lacking TM and CT, about amino acids 522-574 of SEQ ID NOS: 1 or 2), and/or it may have one or more (e.g. , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30) single amino acid mutations (insertions, deletions or substitutions) relative to a natural RSV sequence.
  • RSV F protein e.g., a soluble RSV F protein lacking TM and CT, about amino acids 522-574 of SEQ ID NOS: 1 or 2
  • it may have one or more (e.g. , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30) single amino acid mutations (insertions, deletions or substitutions) relative to a natural RSV sequence.
  • the RSV F protein lacks TM and CT (about amino acids 522-574 of SEQ ID NOS: 1 or 2) and contains one or more (e.g. , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30) single amino acid mutations (insertions, deletions or substitutions) relative to a natural RSV sequence.
  • post-fusion RSV F polypeptides or proteins may contain one or more mutations, for example, mutations that prevent cleavage at one or both of the furin cleavage sites (i.e., amino acids 109 and 136 of SEQ ID NOS: 1 and 2), that prevent cleavage of or introduce trypsin cleavage sites, mutations in the p27 region, and/or mutation in the fusion peptide.
  • Such mutations can prevent aggregation of the soluble polypeptides or proteins and thereby facilitate purifications, can prevent cell-cell fusion if the RSV F protein is expressed on the surface of a cell, such as by expression from a viral replicon (e.g., alphavirus replicon particles), or if the RSV F protein is a component of a virus-like particle.
  • a viral replicon e.g., alphavirus replicon particles
  • furin cleavage mutations include replacement of amino acid residues 106 - 109 of SEQ ID NO: 1 or 2 with RARK (SEQ ID NO: 14), RARQ (SEQ ID NO: 15), QAQN (SEQ ID NO: 16), or IEGR (SEQ ID NO: 17).
  • amino acid residues 133 - 136 of SEQ ID NO: 1 or 2 can be replaced with RKKK (SEQ ID NO: 18), AAAR, QNQN (SEQ ID NO: 19), QQQR (SEQ ID NO:20) or IEGR (SEQ ID NO: 17).
  • RKKK SEQ ID NO: 18
  • AAAR AAAR
  • QNQN SEQ ID NO: 19
  • QQQR SEQ ID NO:20
  • IEGR SEQ ID NO: 17
  • Suitable trypsin cleavage mutations include deletion of any lysine or arginine residue between about position 101 and position 161 of SEQ ID NO: l or 2, or replacement of any such lysine or arginine residue with an amino acid other than lysine or arginine.
  • lysine and/or arginine residues in the p27 region can be substituted or deleted, including deletion of the p27 region in whole or in part.
  • furin mutations can be combined with partial or complete deletion of the fusion peptide region and/or deletion of the HRA or HRB helical region.
  • oligomerization sequences may contain one or more oligomerization sequences.
  • an oligomerization sequence is present, it is preferably a trimerization sequence.
  • Suitable oligomerization sequences include, for example, the coiled coil of the yeast GCN4 leucine zipper protein, trimerizing sequence from bacteriophage T4 fibritin ("foldon"), and the trimer domain of influenza HA. These and other suitable oligomerization sequences are described in greater detail herein.
  • sequence of the carboxy terminus of the RSV F polypeptide or protein, starting from position 480, is
  • GCN PLVFPSDEFDAS ISQVNEKINQSLAF IRKSDELLHNVNDKIEEILSKIYHIENE IARIKKLIGE
  • RSV F polypeptides or proteins that contain a transmembrane region may contain an added amino acid sequence that provides a protease cleavage site.
  • This type of RSV F polypeptide or protein can be produced by expression on the surface of a cell, and recovered in soluble form after cleavage from the cell surface using an appropriate protease.
  • the amino acid sequence that provides a protease cleavage site will be located within about 60 amino acids, about 50 amino acids, about 40 amino acids, about 30 amino acids, about 20 amino acids, about 10 amino acids, or substantially adjacent to the amino terminus of the transmembrane domain (amino acid 525 of SEQ ID NO: l or 2).
  • thrombin cleaves the sequence LVPR (SEQ ID NO:26)
  • factor Xa cleaves the sequence IEGR (SEQ ID NO: 17)
  • enterokinase cleaves the sequence DDDDK (SEQ ID NO:27).
  • Immunogenic polypeptides used according to the invention will usually be isolated or purified. Thus, they will not be associated with molecules with which they are normally, if applicable, found in nature.
  • an F protein used with the invention will not be in the form of a RSV virion (although it may be in the form of an artificial virion, such as a virosome or VLP).
  • Polypeptides will usually be prepared by expression in a recombinant host system. Generally, they (e.g., RSV ecto-domains) are produced by expression of recombinant constructs that encode the ecto-domains in suitable recombinant host cells, although any suitable methods can be used.
  • Suitable recombinant host cells include, for example, insect cells (e.g., Aedes aegypti, Autographa californica, Bombyx mori, Drosophila melanogaster, Spodoptera frugiperda, and Trichoplusia ni), mammalian cells (e.g., human, non-human primate, horse, cow, sheep, dog, cat, and rodent (e.g., hamster), avian cells (e.g., chicken, duck, and geese), bacteria (e.g., E.
  • insect cells e.g., Aedes aegypti, Autographa californica, Bombyx mori, Drosophila melanogaster, Spodoptera frugiperda, and Trichoplusia ni
  • mammalian cells e.g., human, non-human primate, horse, cow, sheep, dog, cat, and rodent (e.g., ham
  • yeast cells e.g., Saccharomyces cerevisiae, Candida albicans, Candida maltosa, Hansenual polymorpha, Kluyveromyces fragilis, Kluyveromyces lactis, Pichia guillerimondii, Pichia pastoris, Schizosaccharomyces pombe and Yarrowia lipolytica
  • Tetrahymena cells e.g., Tetrahymena thermophila
  • Many suitable insect cells and mammalian cells are well-known in the art.
  • Suitable insect cells include, for example, Sf9 cells, Sf21 cells, Tn5 cells, Schneider S2 cells, and High Five cells (a clonal isolate derived from the parental Trichoplusia ni BTI-TN-5B1-4 cell line (Invitrogen)).
  • Suitable mammalian cells include, for example, Chinese hamster ovary (CHO) cells, human embryonic kidney cells (HEK293 cells, typically transformed by sheared adenovirus type 5 DNA), NIH-3T3 cells, 293-T cells, Vero cells, HeLa cells, PERC.6 cells (ECACC deposit number 96022940), Hep G2 cells, MRC-5 (ATCC CCL-171), WI-38 (ATCC CCL-75), fetal rhesus lung cells (ATCC CL-160), Madin-Darby bovine kidney (“MDBK”) cells, Madin-Darby canine kidney (“MDCK”) cells (e.g., MDCK (NBL2), ATCC CCL34; or MDCK 33016, DSM ACC 2219), baby hamster kidney (BHK) cells, such as BHK21-F, HKCC cells, and the like.
  • CHO Chinese hamster ovary
  • HEK293 cells human embryonic kidney cells
  • Suitable avian cells include, for example, chicken embryonic stem cells (e.g., EBx® cells), chicken embryonic fibroblasts, chicken embryonic germ cells, duck cells (e.g., AGE1.CR and AGEl .CR.pIX cell lines (ProBioGen) which are described, for example, in Vaccine 27:4975- 4982 (2009) and WO2005/042728), EB66 cells, and the like.
  • chicken embryonic stem cells e.g., EBx® cells
  • chicken embryonic fibroblasts e.g., chicken embryonic germ cells
  • duck cells e.g., AGE1.CR and AGEl .CR.pIX cell lines (ProBioGen) which are described, for example, in Vaccine 27:4975- 4982 (2009) and WO2005/042728
  • EB66 cells e.g., EB66 cells, and the like.
  • Suitable insect cell expression systems such as baculovirus systems, are known to those of skill in the art and described in, e.g. , Summers and Smith, Texas
  • baculovirus/insert cell expression systems are commercially available in kit form from, inter alia, Invitrogen, San Diego CA.
  • Avian cell expression systems are also known to those of skill in the art and described in, e.g. , U.S. Patent Nos. 5,340,740; 5,656,479; 5,830,510; 6,114,168; and 6,500,668; European Patent No. EP 0787180B; European Patent Application No. EP03291813.8 ;WO 03/043415; and WO 03/076601.
  • bacterial and mammalian cell expression systems are also known in the art and described in, e.g. , Yeast Genetic Engineering (Barr et al , eds., 1989) Butterworths, London.
  • Recombinant constructs encoding pre-fusion RSV F protein can be prepared in suitable vectors using conventional methods.
  • suitable vectors for expression of recombinant proteins in insect or mammalian cells are well-known and conventional in the art.
  • Suitable vectors can contain a number of components, including, but not limited to one or more of the following: an origin of replication; a selectable marker gene; one or more expression control elements, such as a transcriptional control element (e.g., a promoter, an enhancer, a terminator), and/or one or more translation signals; and a signal sequence or leader sequence for targeting to the secretory pathway in a selected host cell (e.g., of mammalian origin or from a heterologous mammalian or non-mammalian species).
  • a suitable baculovirus expression vector such as pFastBac (Invitrogen) is used to produce recombinant baculovirus particles.
  • the baculovirus particles are amplified and used to infect insect cells to express recombinant protein.
  • a vector that will drive expression of the construct in the desired mammalian host cell e.g., Chinese hamster ovary cells.
  • Pre-fusion RSV F protein polypeptides can be purified using any suitable methods. For example, methods for purifying pre-fusion RSV F polypeptides by
  • immunoaffinity chromatography are known in the art. Ruiz-Arguello et al, J. Gen. Virol, ⁇ 5:3677-3687 (2004). Suitable methods for purifying desired proteins including precipitation and various types of chromatography, such as hydrophobic interaction, ion exchange, affinity, chelating and size exclusion are well-known in the art. Suitable purification schemes can be created using two or more of these or other suitable methods.
  • the precision RSV F protein polypeptides can include a "tag" that facilitates purification, such as an epitope tag or a HIS tag. Such tagged polypeptides can conveniently be purified, for example from conditioned media, by chelating chromatography or affinity chromatography.
  • the pre-fusion RSV F polypeptides may also be produced in situ by expression of nucleic acids that encode them in the cells of a subject. For example, by expression of a self-replicating RNA described herein.
  • Polypeptides may include additional sequences in addition to the pre-fusion RSV sequences.
  • a polypeptide may include a sequence to facilitate purification ⁇ e.g., a poly-His sequence).
  • the natural leader peptide of F protein may be substituted for a different one.
  • reference 6 used a honeybee melittin leader peptide in place of the natural one.
  • the pre-fusion RSV-F polypeptides described herein can be produced by expression of recombinant nucleic acids that encode the polypeptides in the cells of a subject.
  • Preferred nucleic acids that can be administered to a subject to cause the production of pre- fusion RSV-F polypeptides are self-replicating RNA molecules.
  • the self -replicating RNA molecules of the invention are based on the genomic RNA of RNA viruses, but lack the genes encoding one or more structural proteins.
  • the self -replicating RNA molecules are capable of being translated to produce non-structural proteins of the RNA virus and heterologous proteins encoded by the self -replicating RNA.
  • the self -replicating RNA generally contains at least one or more genes selected from the group consisting of viral replicase, viral proteases, viral helicases and other nonstructural viral proteins, and also comprise 5'- and 3 '-end cis-active replication sequences, and if desired, a heterologous sequences that encode a desired amino acid sequences (e.g., a protein, an antigen).
  • a subgenomic promoter that directs expression of the heterologous sequence can be included in the self -replicating RNA.
  • the heterologous sequence may be fused in frame to other coding regions in the self-replicating RNA and/or may be under the control of an internal ribosome entry site (IRES).
  • IRS internal ribosome entry site
  • Self -replicating RNA molecules of the invention can be designed so that the self -replicating RNA molecule cannot induce production of infectious viral particles. This can be achieved, for example, by omitting one or more viral genes encoding structural proteins that are necessary for the production of viral particles in the self-replicating RNA.
  • an alpha virus such as Sinebis virus (SIN), Semliki forest virus and Venezuelan equine encephalitis virus (VEE)
  • one or more genes encoding viral structural proteins, such as capsid and/or envelope glycoproteins can be omitted.
  • self -replicating RNA molecules of the invention can be designed to induce production of infectious viral particles that are attenuated or virulent, or to produce viral particles that are capable of a single round of subsequent infection.
  • a self -replicating RNA molecule can, when delivered to a vertebrate cell even without any proteins, lead to the production of multiple daughter RNAs by transcription from itself (or from an antisense copy of itself).
  • the self-replicating RNA can be directly translated after delivery to a cell, and this translation provides a RNA-dependent RNA polymerase which then produces transcripts from the delivered RNA.
  • the delivered RNA leads to the production of multiple daughter RNAs.
  • These transcripts are antisense relative to the delivered RNA and may be translated themselves to provide in situ expression of a gene product, or may be transcribed to provide further transcripts with the same sense as the delivered RNA which are translated to provide in situ expression of the encoded RSV-F polypeptide.
  • One suitable system for achieving self-replication is to use an alphavirus- based RNA replicon.
  • These + stranded replicons are translated after delivery to a cell to give of a replicase (or replicase-transcriptase).
  • the replicase is translated as a polyprotein which auto cleaves to provide a replication complex which creates genomic - strand copies of the + strand delivered RNA.
  • These - strand transcripts can themselves be transcribed to give further copies of the + stranded parent RNA and also to give a subgenomic transcript which encodes the RSV-F polypeptide. Translation of the subgenomic transcript thus leads to in situ expression of the RSV-F polypeptide by the infected cell.
  • Suitable alphavirus replicons can use a replicase from a Sindbis virus, a semliki forest virus, an eastern equine encephalitis virus, a Venezuelan equine encephalitis virus, etc.
  • a preferred self -replicating RNA molecule thus encodes (i) a RNA-dependent RNA polymerase which can transcribe RNA from the self-replicating RNA molecule and (ii) an RSV-F polypeptide.
  • the polymerase can be an alphavirus replicase e.g. comprising alphavirus protein nsP4.
  • an alphavirus based self -replicating RNA molecule of the invention does not encode alphavirus structural proteins.
  • the self replicating RNA can lead to the production of genomic RNA copies of itself in a cell, but not to the production of RNA-containing alphavirus virions.
  • the inability to produce these virions means that, unlike a wild-type alphavirus, the self- replicating RNA molecule cannot perpetuate itself in infectious form.
  • alphavirus structural proteins which are necessary for perpetuation in wild-type viruses are absent from self replicating RNAs of the invention and their place is taken by gene(s) encoding the desired gene product, such that the subgenomic transcript encodes the desired gene product rather than the structural alphavirus virion proteins.
  • a self -replicating RNA molecule useful with the invention may have two open reading frames.
  • the first (5') open reading frame encodes a replicase; the second (3') open reading frame encodes an RSV-F polypeptide.
  • the RNA may have additional (downstream) open reading frames e.g. that encode further desired gene products.
  • a self -replicating RNA molecule can have a 5' sequence which is compatible with the encoded replicase.
  • the self -replicating RNA molecule is derived from or based on an alphavirus.
  • the self -replicating RNA molecule is derived from or based on a virus other than an alphavirus, preferably, a positive-stranded RNA viruses, and more preferably a picornavirus, flavivirus, rubivirus, pestivirus, hepacivirus, calicivirus, or coronavirus.
  • Suitable wild- type alphavirus sequences are well-known and are available from sequence depositories, such as the American Type Culture Collection, Rockville, Md.
  • alphaviruses include Aura (ATCC VR-368), Bebaru virus (ATCC VR-600, ATCC VR-1240), Cabassou (ATCC VR-922), Chikungunya virus (ATCC VR-64, ATCC VR-1241), Eastern equine encephalomyelitis virus (ATCC VR-65, ATCC VR-1242), Fort Morgan (ATCC VR-924), Getah virus (ATCC VR-369, ATCC VR- 1243), Kyzylagach (ATCC VR-927), Mayaro (ATCC VR-66), Mayaro virus (ATCC VR- 1277), Middleburg (ATCC VR-370), Mucambo virus (ATCC VR-580, ATCC VR-1244), Ndumu (ATCC VR-371), Pixuna virus (ATCC VR-372, ATCC VR-1245), Ross River virus (ATCC VR-373, ATCC VR-1246), Semliki Forest (ATCC VR-67, ATCC VR-1247), Sindbis virus (ATCC VR-68, ATCC
  • the self -replicating RNA of the invention are suitable for delivery in a variety of modalities, such as naked RNA delivery or in combination with lipids, polymers or other compounds that facilitate entry into the cells.
  • Self-replicating RNA molecules of the present invention can be introduced into target cells or subjects using any suitable technique, e.g., by direct injection, microinjection, electroporation, lipofection, biolystics, and the like.
  • the self- replicating RNA molecule may also be introduced into cells by way of receptor-mediated endocytosis. See e.g. , U.S. Pat. No. 6,090,619; Wu and Wu, J. Biol.
  • U.S. Pat. No. 6,083,741 discloses introducing an exogenous nucleic acid into mammalian cells by associating the nucleic acid to a polycation moiety (e.g. , poly-L-lysine having 3-100 lysine residues), which is itself coupled to an integrin receptor-binding moiety (e.g. , a cyclic peptide having the sequence Arg-Gly-Asp).
  • a polycation moiety e.g. , poly-L-lysine having 3-100 lysine residues
  • an integrin receptor-binding moiety e.g. , a cyclic peptide having the sequence Arg-Gly-Asp.
  • the self -replicating RNA molecule of the present invention can be delivered into cells via amphiphiles. See e.g., U.S. Pat. No. 6,071 ,890.
  • a nucleic acid molecule may form a complex with the cationic amphiphile. Mammalian cells contacted with the complex can readily take it up.
  • the self -replicating RNA can be delivered as naked RNA (e.g. merely as an aqueous solution of RNA) but, to enhance entry into cells and also subsequent intercellular effects, the self-replicating RNA is preferably administered in combination with a delivery system, such as a particulate or emulsion delivery system.
  • a delivery system such as a particulate or emulsion delivery system.
  • delivery systems include, for example liposome-based delivery (Debs and Zhu (1993) WO 93/24640; Mannino and Gould- Fogerite (1988) BioTechniques 6(7): 682-691 ; Rose U.S. Pat. No.
  • Three particularly useful delivery systems are (i) liposomes (ii) non-toxic and biodegradable polymer microparticles (iii) cationic submicron oil-in-water emulsions.
  • RNA-containing aqueous core can have an anionic, cationic or zwitterionic hydrophilic head group. Formation of liposomes from anionic phospholipids dates back to the 1960s, and cationic liposome-forming lipids have been studied since the 1990s. Some phospholipids are anionic whereas other are zwitterionic.
  • Suitable classes of phospholipid include, but are not limited to, phosphatidylethanolamines, phosphatidylcholines, phosphatidylserines, and phosphatidylglycerols, and some useful phospholipids are listed in Table 2.
  • Useful cationic lipids include, but are not limited to, dioleoyl trimethylammonium propane (DOTAP), l ,2-distearyloxy-N,N-dimethyl-3- aminopropane (DSDMA), l ,2-dioleyloxy-N,Ndimethyl-3-aminopropane (DODMA), 1,2- dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1 ,2-dilinolenyloxy-N,N- dimethyl-3-aminopropane (DLenDMA).
  • DOTAP dioleoyl trimethylammonium propane
  • DSDMA distearyloxy-N,N-dimethyl-3- aminopropane
  • DODMA l ,2-dioleyloxy-N,Ndimethyl-3-aminopropane
  • DLinDMA 1,2- dilinoleyloxy-N,N-
  • Zwitterionic lipids include, but are not limited to, acyl zwitterionic lipids and ether zwitterionic lipids.
  • Examples of useful zwitterionic lipids are DPPC, DOPC and dodecylphosphocholine.
  • the lipids can be saturated or unsaturated.
  • Liposomes can be formed from a single lipid or from a mixture of lipids.
  • a mixture may comprise (i) a mixture of anionic lipids (ii) a mixture of cationic lipids (iii) a mixture of zwitterionic lipids (iv) a mixture of anionic lipids and cationic lipids (v) a mixture of anionic lipids and zwitterionic lipids (vi) a mixture of zwitterionic lipids and cationic lipids or (vii) a mixture of anionic lipids, cationic lipids and zwitterionic lipids.
  • a mixture may comprise both saturated and unsaturated lipids.
  • a mixture may comprise DSPC (zwitterionic, saturated), DlinDMA (cationic, unsaturated), and/or DMPG (anionic, saturated).
  • DSPC zwitterionic, saturated
  • DlinDMA cationic, unsaturated
  • DMPG anionic, saturated
  • the hydrophilic portion of a lipid can be PEGylated (i.e. modified by covalent attachment of a polyethylene glycol). This modification can increase stability and prevent non-specific adsorption of the liposomes.
  • lipids can be conjugated to PEG using techniques such as those disclosed in Heyes et al. (2005) J Controlled Release 107:276-287.
  • a mixture of DSPC, DlinDMA, PEG-DMPG and cholesterol is used in the examples.
  • a separate aspect of the invention is a liposome comprising DSPC, DlinDMA, PEG-DMG and cholesterol.
  • This liposome preferably encapsulates RNA, such as a self- replicating RNA e.g. encoding an immunogen.
  • Liposomes are usually divided into three groups: multilamellar vesicles (MLV); small unilamellar vesicles (SUV); and large unilamellar vesicles (LUV).
  • MLVs have multiple bilayers in each vesicle, forming several separate aqueous compartments.
  • SUVs and LUVs have a single bilayer encapsulating an aqueous core; SUVs typically have a diameter ⁇ 50nm, and LUVs have a diameter >50nm.
  • Liposomes useful with of the invention are ideally LUVs with a diameter in the range of 50-220nm.
  • compositions comprising a population of LUVs with different diameters: (i) at least 80% by number should have diameters in the range of 20-220nm, (ii) the average diameter (Zav, by intensity) of the population is ideally in the range of 40-200nm, and/or (iii) the diameters should have a polydispersity index ⁇ 0.2.
  • Liposomes Methods and Protocols, Volume 1 : Pharmaceutical Nanocarriers: Methods and Protocols, (ed. Weissig). Humana Press, 2009. ISBN 160327359X; Liposome Technology, volumes I, II & III. (ed. Gregoriadis). Informa Healthcare, 2006; and Functional Polymer Colloids and Microparticles volume 4 (Microspheres, microcapsules & liposomes), (eds. Arshady & Guyot). Citus Books, 2002.
  • One useful method involves mixing (i) an ethanolic solution of the lipids (ii) an aqueous solution of the nucleic acid and (iii) buffer, followed by mixing, equilibration, dilution and purification (Heyes et al. (2005) J Controlled Release 107:276-87.).
  • RNA is preferably encapsulated within the liposomes, and so the liposome forms a outer layer around an aqueous RNA-containing core. This encapsulation has been found to protect RNA from RNase digestion.
  • the liposomes can include some external RNA (e.g. on the surface of the liposomes), but at least half of the RNA (and ideally all of it) is encapsulated.
  • RNA molecules can form microparticles to encapsulate or adsorb RNA.
  • the use of a substantially non-toxic polymer means that a recipient can safely receive the particles, and the use of a biodegradable polymer means that the particles can be metabolised after delivery to avoid long-term persistence.
  • Useful polymers are also sterilisable, to assist in preparing pharmaceutical grade formulations.
  • Suitable non-toxic and biodegradable polymers include, but are not limited to, poly(a-hydroxy acids), polyhydroxy butyric acids, polylactones (including
  • polycaprolactones polydioxanones, polyvalerolactone, polyorthoesters, poly anhydrides, polycyanoacrylates, tyrosine-derived polycarbonates, polyvinyl-pyrrolidinones or polyester- amides, and combinations thereof.
  • the microparticles are formed from poly(a-hydroxy acids), such as a poly(lactides) (“PLA”), copolymers of lactide and glycolide such as a poly(D,L-lactide-co-glycolide) (“PLG”), and copolymers of D,L-lactide and caprolactone.
  • PLG polymers include those having a lactide/glycolide molar ratio ranging, for example, from 20:80 to 80:20 e.g. 25:75, 40:60, 45:55, 55:45, 60:40, 75:25.
  • Useful PLG polymers include those having a molecular weight between, for example, 5,000-200,000 Da e.g. between 10,000-100,000, 20,000-70,000, 40,000-50,000 Da.
  • microparticles ideally have a diameter in the range of 0.02 ⁇ to 8 ⁇ .
  • a composition comprising a population of microparticles with different diameters at least 80% by number should have diameters in the range of 0.03-7 ⁇ .
  • a microparticle may include a cationic surfactant and/or lipid e.g.
  • Microparticles of the invention can have a zeta potential of between 40-100 mV.
  • RNA can be adsorbed to the microparticles, and adsorption is facilitated by including cationic materials (e.g. cationic lipids) in the microparticle.
  • cationic materials e.g. cationic lipids
  • Oil-in-water emulsions are known for adjuvanting influenza vaccines e.g. the MF59TM adjuvant in the FLU ADTM product, and the AS03 adjuvant in the PREPANDRIXTM product.
  • RNA delivery according to the present invention can utilise an oil-in-water emulsion, provided that the emulsion includes one or more cationic molecules.
  • a cationic lipid can be included in the emulsion to provide a positive droplet surface to which negatively-charged RNA can attach.
  • the emulsion comprises one or more oils.
  • Suitable oil(s) include those from, for example, an animal (such as fish) or a vegetable source.
  • the oil is ideally biodegradable (metabolisable) and biocompatible.
  • Sources for vegetable oils include nuts, seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil, the most commonly available, exemplify the nut oils.
  • Jojoba oil can be used e.g. obtained from the jojoba bean.
  • Seed oils include safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like.
  • corn oil is the most readily available, but the oil of other cereal grains such as wheat, oats, rye, rice, teff, triticale and the like may also be used.
  • 6-10 carbon fatty acid esters of glycerol and 1 ,2-propanediol, while not occurring naturally in seed oils, may be prepared by hydrolysis, separation and esterification of the appropriate materials starting from the nut and seed oils. Fats and oils from mammalian milk are metabolizable and so may be used. The procedures for separation, purification, saponification and other means necessary for obtaining pure oils from animal sources are well known in the art.
  • cod liver oil cod liver oil
  • shark liver oils and whale oil such as spermaceti exemplify several of the fish oils which may be used herein.
  • a number of branched chain oils are synthesized biochemically in 5-carbon isoprene units and are generally referred to as terpenoids.
  • Squalane the saturated analog to squalene
  • Fish oils including squalene and squalane, are readily available from commercial sources or may be obtained by methods known in the art.
  • oils are the tocopherols, particularly in combination with squalene.
  • the oil phase of an emulsion includes a tocopherol
  • any of the ⁇ , ⁇ , ⁇ , ⁇ , ⁇ or ⁇ tocopherols can be used, but a-tocopherols are preferred.
  • DL-a-tocopherol can both be used.
  • a preferred a-tocopherol is DL-a-tocopherol.
  • An oil combination comprising squalene and a tocopherol (e.g. DL-a-tocopherol) can be used.
  • Preferred emulsions comprise squalene, a shark liver oil which is a branched, unsaturated terpenoid (C30H50; [(C ⁇ C ⁇ CHCHzCHzCCCIL ⁇ CHCHz-k 2,6, 10,15,19,23- hexamethyl-2,6,10,14,18,22-tetracosahexaene; CAS RN 7683-64-9).
  • the oil in the emulsion may comprise a combination of oils e.g. squalene and at least one further oil.
  • the aqueous component of the emulsion can be plain water (e.g. w.f.i.) or can include further components e.g. solutes. For instance, it may include salts to form a buffer e.g. citrate or phosphate salts, such as sodium salts.
  • Typical buffers include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer; or a citrate buffer.
  • a buffered aqueous phase is preferred, and buffers will typically be included in the 5-20mM range.
  • the emulsion also includes a cationic lipid.
  • this lipid is a surfactant so that it can facilitate formation and stabilisation of the emulsion.
  • Useful cationic lipids generally contains a nitrogen atom that is positively charged under physiological conditions e.g. as a tertiary or quaternary amine. This nitrogen can be in the hydrophilic head group of an amphiphilic surfactant.
  • Useful cationic lipids include, but are not limited to: 1,2- dioleoyloxy-3 -(trimethylammonio)propane (DOTAP) , 3 '- [ ⁇ -( ⁇ ' ,N'-Dimethylaminoethane)- carbamoyl] Cholesterol (DC Cholesterol), dimethyldioctadecyl-ammonium (DDA e.g. the bromide), l,2-Dimyristoyl-3-Trimethyl-AmmoniumPropane (DMTAP),
  • DOTAP 1,2- dioleoyloxy-3 -(trimethylammonio)propane
  • DC Cholesterol dimethyldioctadecyl-ammonium
  • DMTAP dimethyldioctadecyl-ammonium
  • Other useful cationic lipids are: benzalkonium chloride (BAK), benzethonium chloride, cetramide (which contains tetradecyltrimethylammonium bromide and possibly small amounts of dedecyltrimethylammonium bromide and hexadecyltrimethyl ammonium bromide), cetylpyridinium chloride (CPC), cetyl trimethylammonium chloride (CTAC), ⁇ , ⁇ ', ⁇ '-polyoxyethylene (10)-N-tallow-l,3 -diaminopropane,
  • BAK benzalkonium chloride
  • cetramide which contains tetradecyltrimethylammonium bromide and possibly small amounts of dedecyltrimethylammonium bromide and hexadecyltrimethyl ammonium
  • dodecyltrimethylammonium bromide dodecyltrimethylammonium bromide, hexadecyltrimethyl-ammonium bromide, mixed alkyl- trimethyl- ammonium bromide, benzyldimethyldodecylammonium chloride,
  • benzyldimethylhexadecyl-ammonium chloride benzyltrimethylammonium methoxide, cetyldimethylethylammonium bromide, dimethyldioctadecyl ammonium bromide (DDAB), methylbenzethonium chloride, decamethonium chloride, methyl mixed trialkyl ammonium chloride, methyl trioctylammonium chloride), N,N-dimethyl-N-[2 (2-methyl-4- (1,1, 3 ,3tetramethylbutyl)- phenoxy] -ethoxy)ethyl] -benzenemetha-naminium chloride
  • acyl group dimyristoyl, dipalmitoyl, distearoyl, dioleoyl), 1,2- dioleoyl-3-(4'-trimethyl- ammonio)butanoyl-sn-glycerol, 1,2-dioleoyl 3 -succinyl-sn- glycerol choline ester, cholesteryl (4'-trimethylammonio) butanoate), N-alkyl pyridinium salts (e.g.
  • cetylpyridinium bromide and cetylpyridinium chloride N-alkylpiperidinium salts, dicationic bolaform electrolytes (C12Me6; C12BU6), dialkylglycetylphosphorylcholine, lysolecithin, L- ⁇ dioleoylphosphatidylethanolamine, cholesterol hemisuccinate choline ester,
  • lipopoly amines including but not limited to dioctadecylamidoglycylspermine (DOGS), dipalmitoyl phosphatidylethanol-amidospermine (DPPES), lipopoly-L (or D)- lysine (LPLL, LPDL), poly (L (or D)-lysine conjugated to N- glutarylphosphatidylethanolamine, didodecyl glutamate ester with pendant amino group (C A GluPhCnN ), ditetradecyl glutamate ester with pendant amino group (C14GIuCnN+), cationic derivatives of cholesterol, including but not limited to cholesteryl-3 ⁇ -oxysuccinamidoethylenetrimethylammonium salt, cholesteryl-3 ⁇ - oxysuccinamidoethylene-dimethylamine, cholesteryl-3 ⁇ - carboxyamidoethylenetrimethylammonium salt, and cholesteryl-3
  • DOGS dioctade
  • the cationic lipid is preferably biodegradable (metabolisable) and
  • an emulsion can include a non-ionic surfactant and/or a zwitterionic surfactant.
  • surfactants include, but are not limited to: the polyoxyethylene sorbitan esters surfactants (commonly referred to as the Tweens), especially polysorbate 20 and polysorbate 80; copolymers of ethylene oxide (EO), propylene oxide (PO), and/or butylene oxide (BO), sold under the DOWFAXTM tradename, such as linear EO/PO block copolymers; octoxynols, which can vary in the number of repeating ethoxy (oxy-l,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, or
  • octylphenoxy polyethoxyethanol
  • phospholipids such as phosphatidylcholine (lecithin); polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such as triethyleneglycol monolauryl ether (Brij 30); polyoxyethylene-9-lauryl ether; and sorbitan esters (commonly known as the Spans), such as sorbitan trioleate (Span 85) and sorbitan monolaurate.
  • Preferred surfactants for including in the emulsion are polysorbate 80 (Tween 80; polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100.
  • Mixtures of these surfactants can be included in the emulsion e.g. Tween 80/Span 85 mixtures, or Tween 80/Triton-X100 mixtures.
  • Tween 80/Span 85 mixtures or Tween 80/Triton-X100 mixtures.
  • Tween 80/Triton-X100 mixtures A combination of a
  • polyoxyethylene sorbitan ester such as polyoxyethylene sorbitan monooleate (Tween 80) and an octoxynol such as t-octylphenoxy-polyethoxyethanol (Triton X-100) is also suitable.
  • Another useful combination comprises laureth 9 plus a polyoxyethylene sorbitan ester and/or an octoxynol.
  • Useful mixtures can comprise a surfactant with a HLB value in the range of 10-20 (e.g. polysorbate 80, with a HLB of 15.0) and a surfactant with a HLB value in the range of 1-10 (e.g. sorbitan trioleate, with a HLB of 1.8).
  • Preferred amounts of oil (% by volume) in the final emulsion are between 2- 20% e.g. 5-15%, 6-14%, 7-13%, 8-12%.
  • a squalene content of about 4-6% or about 9-11 % is particularly useful.
  • Preferred amounts of surfactants (% by weight) in the final emulsion are between 0.001% and 8%.
  • polyoxyethylene sorbitan esters such as polysorbate 80
  • polysorbate 80 0.2 to 4%, in particular between 0.4-0.6%, between 0.45-0.55%, about 0.5% or between 1.5-2%, between 1.8-2.2%, between 1.9-2.1%, about 2%, or 0.85-0.95%, or about 1 %;
  • sorbitan esters such as sorbitan trioleate 0.02 to 2%, in particular about 0.5% or about 1%
  • octyl- or nonylphenoxy polyoxyethanols such as Triton X-100
  • polyoxyethylene ethers such as laureth 9) 0.1 to 8%, preferably 0.1 to 10% and in particular 0.1 to 1% or about 0.5%.
  • the most effective emulsions have a droplet size in the submicron range.
  • the droplet sizes will be in the range 50-750nm.
  • the average droplet size is less than 250nm e.g. less than 200nm, less than 150nm.
  • the average droplet size is usefully in the range of 80-180nm.
  • at least 80% (by number) of the emulsion's oil droplets are less than 250 nm in diameter, and preferably at least 90%.
  • Apparatuses for determining the average droplet size in an emulsion, and the size distribution are commercially available. These typically use the techniques of dynamic light scattering and/or single-particle optical sensing e.g. the
  • AccusizerTM and NicompTM series of instruments available from Particle Sizing Systems (Santa Barbara, USA), or the ZetasizerTM instruments from Malvern Instruments (UK), or the Particle Size Distribution Analyzer instruments from Horiba (Kyoto, Japan).
  • the distribution of droplet sizes has only one maximum i.e. there is a single population of droplets distributed around an average (mode), rather than having two maxima.
  • Preferred emulsions have a polydispersity of ⁇ 0.4 e.g. 0.3, 0.2, or less.
  • Suitable emulsions with submicron droplets and a narrow size distribution can be obtained by the use of microfluidisation.
  • This technique reduces average oil droplet size by propelling streams of input components through geometrically fixed channels at high pressure and high velocity. These streams contact channel walls, chamber walls and each other. The results shear, impact and cavitation forces cause a reduction in droplet size.
  • thermal methods can be used to cause phase inversion. These methods can also provide a submicron emulsion with a tight particle size distribution.
  • Preferred emulsions can be filter sterilized i.e. their droplets can pass through a 220nm filter. As well as providing a sterilization, this procedure also removes any large droplets in the emulsion.
  • the cationic lipid in the emulsion is DOTAP.
  • the cationic oil-in- water emulsion may comprise from about 0.5 mg/ml to about 25 mg/ml DOTAP.
  • the cationic oil-in- water emulsion may comprise DOTAP at from about 0.5 mg/ml to about 25 mg/ml, from about 0.6 mg/ml to about 25 mg/ml, from about 0.7 mg/ml to about 25 mg/ml, from about 0.8 mg/ml to about 25 mg/ml, from about 0.9 mg/ml to about 25 mg/ml, from about 1.0 mg/ml to about 25 mg/ml, from about 1.1 mg/ml to about 25 mg/ml, from about 1.2 mg/ml to about 25 mg/ml, from about 1.3 mg/ml to about 25 mg/ml, from about 1.4 mg/ml to about 25 mg/ml, from about 1.5 mg/ml to about 25 mg/m
  • the cationic oil-in- water emulsion comprises from about 0.8 mg/ml to about 1.6 mg/ml DOTAP, such as 0.8 mg/ml, 1.2 mg/ml, 1.4 mg/ml or 1.6 mg/ml.
  • the cationic lipid is DC Cholesterol.
  • the cationic oil- in-water emulsion may comprise DC Cholesterol at from about 0.1 mg/ml to about 5 mg/ml DC Cholesterol.
  • the cationic oil-in- water emulsion may comprise DC
  • Cholesterol from about 0.1 mg/ml to about 5 mg/ml, from about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5 mg/ml, from about 0.4 mg/ml to about 5 mg/ml, from about 0.5 mg/ml to about 5 mg/ml, from about 0.62 mg/ml to about 5 mg/ml, from about 1 mg/ml to about 5 mg/ml, from about 1.5 mg/ml to about 5 mg/ml, from about 2 mg/ml to about 5 mg/ml, from about 2.46 mg/ml to about 5 mg/ml, from about 3 mg/ml to about 5 mg/ml, from about 3.5 mg/ml to about 5 mg/ml, from about 4 mg/ml to about 5 mg/ml, from about 4.5 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to about 4.92 mg/ml, from about 0.1 mg/ml to about 4.5 mg/
  • the cationic lipid is DDA.
  • the cationic oil-in-water emulsion may comprise from about 0.1 mg/ml to about 5 mg/ml DDA.
  • the cationic oil-in-water emulsion may comprise DDA at from about 0.1 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to about 4.5 mg/ml, from about 0.1 mg/ml to about 4 mg/ml, from about 0.1 mg/ml to about 3.5 mg/ml, from about 0.1 mg/ml to about 3 mg/ml, from about 0.1 mg/ml to about 2.5 mg/ml, from about 0.1 mg/ml to about 2 mg/ml, from about 0.1 mg/ml to about 1.5 mg/ml, from about 0.1 mg/ml to about 1.45 mg/ml, from about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5 mg/ml, from about
  • the cationic oil-in-water emulsion may comprise DDA at about 20 mg/ml, about 21 mg/ml, about 21.5 mg/ml, about 21.6 mg/ml, about 25 mg/ml.
  • the cationic oil-in-water emulsion comprises from about 0.73 mg/ml to about 1.45 mg/ml DDA, such as 1.45 mg/ml.
  • RNA molecules of the invention may be used to deliver the self-replicating RNA molecules of the invention, as naked RNA or in combination with a delivery system, into a target organ or tissue.
  • Suitable catheters are disclosed in, e.g. , U.S. Pat. Nos. 4,186,745; 5,397,307; 5,547,472; 5,674, 192; and 6, 129,705, all of which are incorporated herein by reference.
  • the present invention includes the use of suitable delivery systems, such as liposomes, polymer microparticles or submicron emulsion microparticles with encapsulated or adsorbed self-replicating RNA, to deliver a self-replicating RNA molecule that encodes an RSV-F polypeptide, for example, to elicit an immune response alone, or in combination with another macromolecule.
  • suitable delivery systems such as liposomes, polymer microparticles or submicron emulsion microparticles with encapsulated or adsorbed self-replicating RNA, to deliver a self-replicating RNA molecule that encodes an RSV-F polypeptide, for example, to elicit an immune response alone, or in combination with another macromolecule.
  • the invention includes liposomes, microparticles and submicron emulsions with adsorbed and/or encapsulated self-replicating RNA molecules, and combinations thereof.
  • the self-replicating RNA molecules associated with liposomes and submicron emulsion microparticles can be effectively delivered to the host cell, and can induce an immune response to the protein encoded by the self-replicating RNA.
  • the invention provides immunogenic compositions.
  • the immunogenic compositions may include a single active immunogenic agent, or several immunogenic agents.
  • the immunogenic composition can comprise pre-fusion RSV F polypeptides or a combination of pre-fusion chimeric RSV F polypeptides.
  • immunogenic composition can comprise a self-replicating RNA encoding a pre-fusion RSV- F polypeptide, and preferably also comprises a suitable delivery system, such as liposomes, polymeric microparticles, an oil-in-water emulsion and combinations thereof.
  • a suitable delivery system such as liposomes, polymeric microparticles, an oil-in-water emulsion and combinations thereof.
  • Immunogenic compositions of the invention may also comprise one or more immunoregulatory agents.
  • one or more of the immunoregulatory agents include one or more adjuvants, for example two, three, four or more adjuvants.
  • the adjuvants may include a TH1 adjuvant and/or a TH2 adjuvant, further discussed below.
  • an immunogenic composition of the invention comprises a polypeptide that displays an epitope present in a pre-fusion conformation of RSV-F glycoprotein.
  • an immunogenic composition of the invention comprises one or more pre-fusion chimera proteins based on two different pre-fusion non- RSV (F proteins (e.g, metapneumo virus, parainfluenza, such asPIV5, NDV), in which both have the same RSV F neutralizing epitopes mutated on the protein surface.
  • F proteins e.g, metapneumo virus, parainfluenza, such asPIV5, NDV
  • compositions of the invention are preferably suitable for administration to a mammalian subject, such as a human, and include one or more pharmaceutically acceptable carrier(s) and/or excipient(s), including adjuvants.
  • a mammalian subject such as a human
  • compositions will generally be in aqueous form.
  • the composition is an immunogenic composition, it will elicit an immune response when administered to a mammal, such as a human.
  • the immunogenic composition can be used to prepare a vaccine formulation for immunizing a mammal.
  • the immunogenic compositions may include a single active immunogenic agent, or several immunogenic agents.
  • the pre-fusion RSV F protein can be full length or a ecto-domain polypeptide and can be in a single form (e.g., uncleaved monomer, cleaved monomer, uncleaved trimer, cleaved trimer) or in two or more forms (e.g., a mixture of uncleaved monomer and uncleaved trimer or a dynamic equilibrium between uncleaved monomer and uncleaved trimer).
  • the compositions can contain a pre-fusion RSV F protein and one or more other RSV proteins (e.g., a G protein and/or an M protein) and/or it may be combined with immunogens from other pathogens.
  • the composition may include preservatives such as thiomersal or 2- phenoxyethanol. It is preferred, however, that the vaccine should be substantially free from (i.e. , less than 5 ⁇ g/ml) mercurial material, e.g. , thiomersal-free. Immunogenic compositions containing no mercury are more preferred. Preservative-free immunogenic compositions are particularly preferred.
  • a physiological salt such as a sodium salt. Sodium chloride (NaCl) is preferred, which may be present at between 1 and 20 mg/ml.
  • Other salts that may be present include potassium chloride, potassium dihydrogen phosphate, disodium phosphate dehydrate, magnesium chloride, calcium chloride, and the like.
  • compositions will generally have an osmolality of between 200 mOsm/kg and 400 mOsm/kg, preferably between 240-360 mOsm/kg, and will more preferably fall within the range of 290-310 mOsm/kg.
  • Compositions may include one or more buffers.
  • Typical buffers include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer
  • a process of the invention may therefore include a step of adjusting the pH of the bulk vaccine prior to packaging.
  • the composition is preferably sterile.
  • the composition is preferably non-pyrogenic, e.g., containing ⁇ 1 EU (endotoxin unit, a standard measure) per dose, and preferably ⁇ 0.1 EU per dose.
  • the composition is preferably gluten free.
  • Human vaccines are typically administered in a dosage volume of about 0.5ml, although a half dose (i.e., about 0.25ml) may be administered to children.
  • compositions of the invention that contain RSV-F polypeptides, or nucleic acids that encode RSV-F polypeptides, may also include one or more adjuvants, for example two, three, four or more adjuvants, which can function to enhance the immune responses (humoral and/or cellular) elicited in a patient who receives the composition.
  • the adjuvants may include a TH1 adjuvant and/or a TH2 adjuvant.
  • Adjuvants which may be used in compositions of the invention include, but are not limited to:
  • Mineral-containing compositions suitable for use as adjuvants in the invention include mineral salts, such as calcium salts and aluminum salts (or mixtures thereof).
  • the invention includes mineral salts such as hydroxides (e.g. oxyhydroxides), phosphates (e.g. hydroxyphosphates, orthophosphates), sulphates, etc. , or mixtures of different mineral compounds, with the compounds taking any suitable form (e.g. gel, crystalline, amorphous, etc.), and with adsorption being preferred.
  • Calcium salts include calcium phosphate (e.g., the "CAP" particles disclosed in ref. 38).
  • Aluminum salts include hydroxides, phosphates, sulfates, and the like.
  • the mineral containing compositions may also be formulated as a particle of metal salt (39). Aluminum salt adjuvants are described in more detail below.
  • Oil emulsion compositions (see in more detail below).
  • Oil emulsion compositions suitable for use as adjuvants in the invention include squalene-water emulsions, such as MF59 (5% Squalene, 0.5% Tween 80 and 0.5% Span, formulated into submicron particles using a microfluidizer).
  • squalene-water emulsions such as MF59 (5% Squalene, 0.5% Tween 80 and 0.5% Span, formulated into submicron particles using a microfluidizer).
  • Cytokine-inducing agents include toll-like receptor 7 (TLR7) agonists (e.g. benzonaphthyridine compounds disclosed in WO 2009/111337.
  • TLR7 toll-like receptor 7
  • Saponins (chapter 22 of ref. 74), which are a heterologous group of sterol glycosides and triterpenoid glycosides that are found in the bark, leaves, stems, roots and even flowers of a wide range of plant species. Saponin from the bark of the Quillaia saponaria Molina tree have been widely studied as adjuvants. Saponin can also be commercially obtained from Smilax ornata (sarsaprilla), Gypsophilla paniculata (brides veil), and Saponaria officianalis (soap root). Saponin adjuvant formulations include purified formulations, such as QS21, as well as lipid formulations, such as ISCOMs.
  • QS21 is marketed as STIMULON (TM).
  • Saponin compositions have been purified using HPLC and RP-HPLC. Specific purified fractions using these techniques have been identified, including QS7, QS17, QS18, QS21, QH-A, QH-B and QH-C.
  • the saponin is QS21.
  • a method of production of QS21 is disclosed in ref. 40.
  • Saponin formulations may also comprise a sterol, such as cholesterol (41). Combinations of saponins and cholesterols can be used to form unique particles called immunostimulating complexes (ISCOMs) (chapter 23 of ref. 74).
  • ISCOMs immunostimulating complexes
  • ISCOMs typically also include a phospholipid such as phosphatidylethanolamine or phosphatidylcholine. Any known saponin can be used in ISCOMs.
  • the ISCOM includes one or more of QuilA, QHA & QHC. ISCOMs are further described in refs. 41-43.
  • the ISCOMS may be devoid of additional detergent (44). A review of the development of saponin based adjuvants can be found in refs. 45 & 46.
  • Fatty adjuvants including oil-in-water emulsions, modified natural lipid As derived from enterobacterial lipopolysaccharides, phospholipid compounds (such as the synthetic phospholipid dimer, E6020) and the like.
  • Bacterial ADP-ribosylating toxins e.g., the E. coli heat labile enterotoxin "LT”, cholera toxin "CT”, or pertussis toxin "PT” and detoxified derivatives thereof, such as the mutant toxins known as LT-K63 and LT-R72 (47).
  • the use of detoxified ADP- ribosylating toxins as mucosal adjuvants is described in ref. 48 and as parenteral adjuvants in ref. 49.
  • Bioadhesives and mucoadhesives such as esterified hyaluronic acid microspheres (50) or chitosan and its derivatives (51).
  • Microparticles i.e., a particle of -100 nm to -150 ⁇ in diameter, more preferably -200 nm to -30 ⁇ in diameter, or -500 nm to -10 ⁇ in diameter
  • materials that are biodegradable and non-toxic e.g., a poly(a-hydroxy acid), a polyhydroxybutyric acid, a polyorthoester, a polyanhydride, a polycaprolactone, and the like
  • poly(lactide-co-glycolide) being preferred, optionally treated to have a negatively-charged surface (e.g., with SDS) or a positively-charged surface (e.g., with a cationic detergent, such as CTAB).
  • Liposomes Chosomes 13 & 14 of ref. 74. Examples of liposome formulations suitable for use as adjuvants are described in refs. 52-54.
  • Polyoxyethylene ethers and polyoxyethylene esters (55). Such formulations further include polyoxyethylene sorbitan ester surfactants in combination with an octoxynol (56) as well as polyoxyethylene alkyl ethers or ester surfactants in combination with at least one additional non-ionic surfactant such as an octoxynol (57).
  • Preferred polyoxyethylene ethers are selected from the following group: polyoxyethylene-9- lauryl ether (laureth 9), polyoxyethylene-9-steoryl ether, polyoxytheylene-8-steoryl ether, polyoxyethylene-4-lauryl ether, polyoxyethylene-35-lauryl ether, and polyoxyethylene-23-lauryl ether.
  • Muramyl peptides such as N-acetylmuramyl-L-threonyl-D-isoglutamine (“thr- MDP"), N-acetyl-normuramyl-L-alanyl-D-isoglutamine (nor-MDP), N- acetylglucsaminyl-N-acetylmuramyl-L-Al-D-isoglu-L-Ala-dipalmitoxy propylamide ("DTP-DPP", or "TheramideTM), N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L- alanine-2-(l'-2'dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine (“MTP- PE").
  • thr- MDP N-acetylmuramyl-L-threonyl-D-isoglutamine
  • An outer membrane protein proteosome preparation prepared from a first Gram- negative bacterium in combination with a liposaccharide preparation derived from a second Gram-negative bacterium, wherein the outer membrane protein proteosome and liposaccharide preparations form a stable non-covalent adjuvant complex.
  • Such complexes include "IVX-908", a complex comprised of Neisseria meningitidis outer membrane and lipopolysaccharides.
  • a polyoxidonium polymer (58, 59) or other N-oxidized polyethylene-piperazine derivative is added.
  • MIMP Methyl inosine 5 '-monophosphate
  • a CD Id ligand such as an a-glycosylceramide (62-69) ⁇ e.g., a-galactosylceramide), phytosphingosine-containing a-glycosylceramides, OCH, KRN7000 [(2S,3S,4R)-1- 0-(a-D-galactopyranosyl)-2-(N-hexacosanoylamino)-l,3,4-octadecanetriol],
  • Virosomes and virus-like particles These structures generally contain one or more proteins from a virus optionally combined or formulated with a phospholipid. They are generally non-pathogenic, non-replicating and generally do not contain any of the native viral genome. The viral proteins may be recombinantly produced or isolated from whole viruses.
  • viral proteins suitable for use in virosomes or VLPs include proteins derived from influenza virus (such as HA or NA), Hepatitis B virus (such as core or capsid proteins), Hepatitis E virus, measles virus, Sindbis virus, Rotavirus, Foot-and- Mouth Disease virus, Retrovirus, Norwalk virus, human Papilloma virus, HIV, RNA- phages, Q6-phage (such as coat proteins), GA-phage, fr-phage, AP205 phage, and Ty (such as retrotransposon Ty protein pi).
  • influenza virus such as HA or NA
  • Hepatitis B virus such as core or capsid proteins
  • Hepatitis E virus measles virus
  • Sindbis virus Rotavirus
  • Foot-and- Mouth Disease virus Retrovirus
  • Norwalk virus Norwalk virus
  • human Papilloma virus HIV
  • RNA- phages such as coat proteins
  • GA-phage f-phage
  • fr-phage AP205
  • compositions may include two, three, four or more adjuvants.
  • compositions of the invention may advantageously include both an oil-in- water emulsion and a cytokine-inducing agent, or both a mineral-containing composition and a cytokine-inducing agent, or two oil-in-water emulsion adjuvants, or two benzonaphthyridine compounds, etc.
  • Antigens and adjuvants in a composition will typically be in admixture.
  • Oil emulsion compositions suitable for use as adjuvants in the invention include squalene-water emulsions, such as MF59 (5% Squalene, 0.5% Tween 80, and 0.5% Span 85, formulated into submicron particles using a microfluidizer). Complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IF A) may also be used.
  • CFA Complete Freund's adjuvant
  • IF A incomplete Freund's adjuvant
  • oil-in- water emulsions typically include at least one oil and at least one surfactant, with the oil(s) and surfactant(s) being biodegradable (metabolizable) and biocompatible.
  • the oil droplets in the emulsion are generally less than 5 ⁇ in diameter, and may even have a sub-micron diameter, with these small sizes being achieved with a microfluidizer to provide stable emulsions. Droplets with a size less than 220 nm are preferred as they can be subjected to filter sterilization.
  • the invention can be used with oils such as those from an animal (such as fish) or vegetable source.
  • Sources for vegetable oils include nuts, seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil, the most commonly available, exemplify the nut oils.
  • Jojoba oil can be used, e.g., obtained from the jojoba bean.
  • Seed oils include safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like. In the grain group, corn oil is the most readily available, but the oil of other cereal grains such as wheat, oats, rye, rice, teff, triticale and the like may also be used.
  • 6-10 carbon fatty acid esters of glycerol and 1 ,2-propanediol may be prepared by hydrolysis, separation and esterification of the appropriate materials starting from the nut and seed oils.
  • Fats and oils from mammalian milk are metabolizable and may therefore be used in the practice of this invention.
  • the procedures for separation, purification, saponification and other means necessary for obtaining pure oils from animal sources are well known in the art.
  • Most fish contain metabolizable oils which may be readily recovered. For example, cod liver oil, shark liver oils, and whale oil such as spermaceti exemplify several of the fish oils which may be used herein.
  • a number of branched chain oils are synthesized biochemically in 5- carbon isoprene units and are generally referred to as terpenoids.
  • Shark liver oil contains a branched, unsaturated terpenoid known as squalene, 2,6,10,15, 19, 23-hexamethyl- 2,6,10,14,18,22-tetracosahexaene, which is particularly preferred herein.
  • Squalane the saturated analog to squalene
  • Fish oils, including squalene and squalane are readily available from commercial sources or may be obtained by methods known in the art. Other preferred oils are the tocopherols (see below). Mixtures of oils can be used.
  • Surfactants can be classified by their 'HLB' (hydrophile/lipophile balance). Preferred surfactants of the invention have a HLB of at least 10, preferably at least 15, and more preferably at least 16.
  • the invention can be used with surfactants including, but not limited to: the polyoxyethylene sorbitan esters surfactants (commonly referred to as the Tweens), especially polysorbate 20 and polysorbate 80; copolymers of ethylene oxide (EO), propylene oxide (PO), and/or butylene oxide (BO), sold under the DOWFAX (TM) tradename, such as linear EO/PO block copolymers; octoxynols, which can vary in the number of repeating ethoxy (oxy-l,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, or t-octylphenoxypolyethoxyethanol) being of particular interest;
  • Tweens polyoxyethylene sorb
  • octylphenoxy polyethoxyethanol
  • IGEPAL CA-630/NP-40 phospholipids such as phosphatidylcholine (lecithin); nonylphenol ethoxylates, such as the TERGITOL (TM) NP series; polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such as triethyleneglycol monolauryl ether (Brij 30); and sorbitan esters (commonly known as the SPANs), such as sorbitan trioleate (Span 85) and sorbitan monolaurate.
  • Non-ionic surfactants are preferred.
  • Preferred surfactants for including in the emulsion are TWEEN 80 (TM) (polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100.
  • TWEEN 80 (TM)/Span 85 mixtures Mixtures of surfactants can be used e.g., TWEEN 80 (TM)/Span 85 mixtures.
  • a combination of a polyoxyethylene sorbitan ester such as polyoxyethylene sorbitan monooleate (TWEEN 80 (TM)) and an octoxynol such as t-octylphenoxypolyethoxyethanol (Triton X-100) is also suitable.
  • Another useful combination comprises laureth 9 plus a polyoxyethylene sorbitan ester and/or an octoxynol.
  • Preferred amounts of surfactants are: polyoxyethylene sorbitan esters (such as TWEEN 80 (TM)) 0.01 to 1 %, in particular about 0.1 %; octyl- or
  • nonylphenoxy polyoxyethanols such as Triton X-100, or other detergents in the Triton series
  • polyoxyethylene ethers such as laureth 9
  • laureth 9 polyoxyethylene ethers
  • oil-in-water emulsion adjuvants useful with the invention include, but are not limited to:
  • a submicron emulsion of squalene, TWEEN 80 (TM), and Span 85 The composition of the emulsion by volume can be about 5% squalene, about 0.5% polysorbate 80 and about 0.5% Span 85. In weight terms, these ratios become 4.3% squalene, 0.5% polysorbate 80 and 0.48% Span 85.
  • This adjuvant is known as 'MF59' (71-73), as described in more detail in Chapter 10 of ref. 74 and chapter 12 of ref. 75.
  • the MF59 emulsion advantageously includes citrate ions, e.g., lOmM sodium citrate buffer.
  • the emulsion may include phosphate buffered saline. It may also include Span 85 (e.g., at 1 %) and/or lecithin. These emulsions may have from 2 to 10% squalene, from 2 to 10% tocopherol and from 0.3 to 3% TWEEN 80 (TM), and the weight ratio of squalene tocopherol is preferably ⁇ 1 as this provides a more stable emulsion. Squalene and TWEEN 80 (TM) may be present volume ratio of about 5:2.
  • One such emulsion can be made by dissolving TWEEN 80 (TM) in PBS to give a 2% solution, then mixing 90ml of this solution with a mixture of (5g of DL-a-tocopherol and 5ml squalene), then microfluidizing the mixture.
  • the resulting emulsion may have submicron oil droplets, e.g., with an average diameter of between 100 and 250nm, preferably about 180nm.
  • An emulsion of squalene, a tocopherol, and a Triton detergent e.g., Triton X-100.
  • the emulsion may also include a 3d-MPL (see below).
  • the emulsion may contain a phosphate buffer.
  • An emulsion comprising a polysorbate (e.g., polysorbate 80), a Triton detergent (e.g., Triton X-100) and a tocopherol (e.g., an a-tocopherol succinate).
  • the emulsion may include these three components at a mass ratio of about 75: 11 : 10 (e.g., 750 ⁇ g/ml polysorbate 80, 110 ⁇ g/ml Triton X-100 and 100 ⁇ g/ml ⁇ -tocopherol succinate), and these concentrations should include any contribution of these components from antigens.
  • the emulsion may also include squalene.
  • the emulsion may also include a 3d-MPL (see below).
  • the aqueous phase may contain a phosphate buffer.
  • An emulsion of squalane, polysorbate 80 and poloxamer 401 (“PLURONIC (TM) L121").
  • the emulsion can be formulated in phosphate buffered saline, pH 7.4.
  • This emulsion is a useful delivery vehicle for muramyl dipeptides, and has been used with threonyl-MDP in the "SAF-1" adjuvant (76) (0.05-1 % Thr-MDP, 5% squalane, 2.5% Pluronic L121 and 0.2% polysorbate 80). It can also be used without the Thr-MDP, as in the "AF' adjuvant (77) (5% squalane, 1.25% Pluronic L121 and 0.2% polysorbate 80). Microfluidization is preferred.
  • An emulsion comprising squalene, an aqueous solvent, a polyoxyethylene alkyl ether hydrophilic nonionic surfactant (e.g. polyoxyethylene (12) cetostearyl ether) and a hydrophobic nonionic surfactant (e.g. a sorbitan ester or mannide ester, such as sorbitan monoleate or 'Span 80') ⁇
  • the emulsion is preferably thermoreversible and/or has at least 90% of the oil droplets (by volume) with a size less than 200 nm.
  • the emulsion may also include one or more of: alditol; a cryoprotective agent (e.g. a sugar, such as dodecylmaltoside and/or sucrose); and/or an alky lpoly glycoside. Such emulsions may be lyophilized.
  • An emulsion having from 0.5-50% of an oil, 0.1-10% of a phospholipid, and 0.05-5% of a non- ionic surfactant.
  • preferred phospholipid components are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cardiolipin. Submicron droplet sizes are advantageous.
  • Additives may be included, such as QuilA saponin, cholesterol, a saponin-lipophile conjugate (such as GPI-0100, described in reference 79, produced by addition of aliphatic amine to desacylsaponin via the carboxyl group of glucuronic acid), dimethyidioctadecylammonium bromide and/or N,N-dioctadecyl-N,N-bis (2- hydroxyethyl)propanediamine.
  • a non-metabolizable oil such as light mineral oil
  • surfactant such as lecithin, TWEEN 80 (TM) or Span 80.
  • Additives may be included, such as QuilA saponin, cholesterol, a saponin-lip
  • An emulsion comprising a mineral oil, a non-ionic lipophilic ethoxylated fatty alcohol, and a non- ionic hydrophilic surfactant (e.g. an ethoxylated fatty alcohol and/or poly oxye thy lene-polyoxypropylene block copolymer).
  • a non-ionic lipophilic ethoxylated fatty alcohol e.g. an ethoxylated fatty alcohol and/or poly oxye thy lene-polyoxypropylene block copolymer
  • An emulsion comprising a mineral oil, a non-ionic hydrophilic ethoxylated fatty alcohol, and a non-ionic lipophilic surfactant (e.g. an ethoxylated fatty alcohol and/or poly oxye thy lene-polyoxypropylene block copolymer).
  • a saponin e.g., QuilA or QS21
  • a sterol e.g., a cholesterol
  • the emulsions may be mixed with antigen extemporaneously, at the time of delivery.
  • the adjuvant and antigen may be kept separately in a packaged or distributed vaccine, ready for final formulation at the time of use.
  • the antigen will generally be in an aqueous form, such that the vaccine is finally prepared by mixing two liquids.
  • the volume ratio of the two liquids for mixing can vary (e.g., between 5: 1 and 1 :5) but is generally about 1 : 1.
  • Cytokine-inducing agents for inclusion in compositions of the invention are able, when administered to a patient, to elicit the immune system to release cytokines, including interferons and interleukins.
  • Preferred agents can elicit the release of one or more of: interferon- ⁇ ; interleukin-1 ; interleukin-2; interleukin-12; TNF-a; TNF- ⁇ ; and GM-CSF.
  • Preferred agents elicit the release of cytokines associated with a Thl-type immune response, e.g., interferon- ⁇ , TNF-a, interleukin-2. Stimulation of both interferon- ⁇ and interleukin-2 is preferred.
  • a patient will have T cells that, when stimulated with a RSV F protein, will release the desired cytokine(s) in an antigen-specific manner.
  • T cells purified from their blood will release ⁇ -interferon when exposed in vitro to F protein.
  • Methods for measuring such responses in peripheral blood mononuclear cells (PBMC) are known in the art, and include ELISA, ELISPOT, flow-cytometry and real-time PCR.
  • reference 81 reports a study in which antigen-specific T cell-mediated immune responses against tetanus toxoid, specifically ⁇ -interferon responses, were monitored, and found that ELISPOT was the most sensitive method to discriminate antigen-specific TT-induced responses from spontaneous responses, but that intracytoplasmic cytokine detection by flow cytometry was the most efficient method to detect re-stimulating effects.
  • Suitable cytokine-inducing agents include, but are not limited to:
  • An immunostimulatory oligonucleotide such as one containing a CpG motif (a dinucleotide sequence containing an unmethylated cytosine linked by a phosphate bond to a guanosine), or a double-stranded RNA, or an oligonucleotide containing a palindromic sequence, or an oligonucleotide containing a poly(dG) sequence.
  • An imidazoquinoline compound such as IMIQUIMOD (TM) ("R-837”) (86, 87), RESIQUIMOD (TM) ("R-848”) (88), and their analogs; and salts thereof ⁇ e.g., the hydrochloride salts). Further details about immunostimulatory imidazoquinolines can be found in references 89 to 93.
  • a benzonaphthyridine compound such as: (a) a compound having the formula: wherein:
  • R 4 is selected from H, halogen, -C(0)OR 7 , -C(0)R 7 , -C(0)N(R n R 12 ), -N(R n R 12 ), -N(R 9 ) 2 , -NHN(R 9 ) 2 , -SR 7 , -(CH 2 ) n OR 7 , -(CH 2 ) n R 7 ,
  • Ci-C6haloalkoxy aryl, heteroaryl, C3-Cscycloalkyl
  • C3-Csheterocycloalkyl groups of R 4 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, -N0 2 , -R 7 , - OR 8 , -C(0)R 8 , -OC(0)R 8 , -C(0)OR 8 , -N(R 9 ) 2 , -P(0)(OR 8 ) 2 , - OP(0)(OR 8 ) 2 , -P(O)(OR 10 ) 2 ,
  • each L is independently selected from a bond, -(0(CH2) m )r, Ci-C6alkyl,
  • C2-C6alkenylene and C2-C6alkynylene of L are each optionally substituted with 1 to 4 substituents independently selected from halogen, -R 8 , -OR 8 , - N(R 9 ) 2 , -P(0)(OR 8 ) 2 , -OP(0)(OR 8 ) 2 ,
  • R 7 is selected from H, Ci-C 6 alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
  • Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl wherein the Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
  • Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl groups of R 7 are each optionally substituted with 1 to 3 R 13 groups;
  • each R 8 is independently selected from H, -CH(R 10 )2, Ci-Csalkyl,
  • Ci-C6heteroalkyl C3-Cscycloalkyl, C2-Csheterocycloalkyl,
  • Ci-C6hydroxyalkyl and Ci-C6haloalkoxy wherein the Ci-Csalkyl, C2- Csalkene, C2-Csalkyne, Ci-C6heteroalkyl, Ci-C6haloalkyl,
  • Ci-C6hydroxyalkyl and Ci-C6haloalkoxy groups of R 8 are each optionally substituted with 1 to 3 substituents independently selected from -CN, R 11 , -OR 11 , -SR 11 , -C(0)R n , -OC(0)R n ,
  • ch R 9 is independently selected from H, -C(0)R 8 , -C(0)OR 8 , -C(0)R 10 ,
  • each R 9 is independently a Ci-C6alkyl that together with N they are attached to form a C3-Csheterocycloalkyl, wherein the C 3 - Csheterocycloalkyl ring optionally contains an additional heteroatom selected from N, O and S, and wherein the Ci-C 6 alkyl, Ci-C 6 heteroalkyl, C3-C6 cycloalkyl, or
  • C3-Csheterocycloalkyl groups of R 9 are each optionally substituted with 1 to 3 substituents independently selected from
  • ch R 10 is independently selected from aryl, C3-Cscycloalkyl,
  • C3-C 8 cycloalkyl, C3-Csheterocycloalkyl and heteroaryl groups are optionally substituted with 1 to 3 substituents selected from halogen, -R 8 , - OR 8 , -LR 9 , -LOR 9 , -N(R 9 ) 2 , -NR 9 C(0)R 8 ,
  • R 12 are independently selected from H, Ci-C6alkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, aryl, heteroaryl,
  • Ci-C6alkyl, Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl, C3- Cscycloalkyl, and C3-Csheterocycloalkyl groups of R 11 and R 12 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, R 8 , -OR 8 , -C(0)R 8 ,
  • R 11 and R 12 are each independently Ci-C6alkyl and taken together with the N atom to which they are attached form an optionally substituted C 3 - Csheterocycloalkyl ring optionally containing an additional heteroatom selected from N, O and S; each R 13 is independently selected from halogen, -CN, -LR 9 , -LOR 9 ,
  • each R A is independently selected from -R 8 , -R 7 , -OR 7 , -OR 8 , -R 10 ,
  • n is, independently at each occurrence, 0, 1, 2, 3, 4, 5, 6, 7 or 8;
  • each m is independently selected from 1, 2, 3, 4, 5 and 6, and
  • t 1, 2, 3, 4, 5, 6, 7 or 8;
  • R 4 is selected from H, halogen, -C(0)OR 7 , -C(0)R 7 , -C(0)N(R n R 12 ),
  • Ci-Cehaloalkyl C 2 -Csalkene, C 2 -Csalkyne, Ci-C 6 alkoxy, Ci-C6haloalkoxy, aryl, heteroaryl, C3-Cscycloalkyl, and C3- Csheterocycloalkyl, wherein the Ci-C 6 alkyl, Ci-C6heteroalkyl, d- Cehaloalkyl, C 2 -Csalkene, C 2 -Csalkyne, Ci-C6alkoxy,
  • Ci-C6haloalkoxy aryl, heteroaryl, C3-Cscycloalkyl
  • C3-Csheterocycloalkyl groups of R 4 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, -N0 2 , -R 7 , - OR 8 , -C(0)R 8 , -OC(0)R 8 , -C(0)OR 8 , -N(R 9 ) 2 , -P(0)(OR 8 ) 2 , - OP(0)(OR 8 ) 2 , -P(O)(OR 10 ) 2 ,
  • each L is independently selected from a bond, -(0(CH 2 ) m ) r , Ci-C6alkyl, C 2 - C 6 alkenylene and C 2 -C6alkynylene, wherein the Ci-C6alkyl, C 2 - C 6 alkenylene and C 2 -C 6 alkynylene of L are each optionally substituted with 1 to 4 substituents independently selected from halogen, -R 8 , -OR 8 , - N(R 9 ) 2 , -P(0)(OR 8 ) 2 , -OP(0)(OR 8 ) 2 ,
  • R 7 is selected from H, Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, C 2 -Csalkene, C 2 -Csalkyne,
  • Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl wherein the Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, C 2 -Csalkene, C 2 -Csalkyne,
  • Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl groups of R 7 are each optionally substituted with 1 to 3 R 13 groups;
  • each R 8 is independently selected from H, -CH(R 10 ) 2 , Ci-Csalkyl,
  • Ci-C6heteroalkyl C3-Cscycloalkyl, C 2 -Csheterocycloalkyl,
  • Ci-C6hydroxyalkyl and Ci-C6haloalkoxy wherein the Ci-Csalkyl, C 2 - Csalkene, C 2 -Csalkyne, Ci-C6heteroalkyl, Ci-C6haloalkyl,
  • Ci-C6hydroxyalkyl and Ci-C6haloalkoxy groups of R 8 are each optionally substituted with 1 to 3 substituents independently selected from -CN, R 11 , -OR 11 , -SR 11 , -C(0)R n , -OC(0)R n ,
  • ch R 9 is independently selected from H, -C(0)R 8 , -C(0)OR 8 , -C(0)R 10 , - C(0)OR 10 , -S(0) 2 R 10 , -Ci-C 6 alkyl, Ci-C 6 heteroalkyl and C 3 -C 6 cycloalkyl, or each R 9 is independently a Ci-C6alkyl that together with N they are attached to form a C3-Csheterocycloalkyl, wherein the C 3 - Csheterocycloalkyl ring optionally contains an additional heteroatom selected from N, O and S, and wherein the Ci-C 6 alkyl, Ci-C 6 heteroalkyl, C3-C6 cycloalkyl, or
  • C3-Csheterocycloalkyl groups of R 9 are each optionally substituted with 1 to 3 substituents independently selected from
  • ch R 10 is independently selected from aryl, C3-Cscycloalkyl,
  • C3-C 8 cycloalkyl, C3-Csheterocycloalkyl and heteroaryl groups are optionally substituted with 1 to 3 substituents selected from halogen, -R 8 , - OR 8 , -LR 9 , -LOR 9 , -N(R 9 ) 2 , -NR 9 C(0)R 8 ,
  • R 12 are independently selected from H, Ci-C6alkyl,
  • Ci-C6heteroalkyl Ci-C6haloalkyl, aryl, heteroaryl,
  • Ci-C6alkyl, Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl, C3- Cscycloalkyl, and C3-Csheterocycloalkyl groups of R 11 and R 12 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, R 8 , -OR 8 , -C(0)R 8 ,
  • R 11 and R 12 are each independently Ci-C6alkyl and taken together with the N atom to which they are attached form an optionally substituted C 3 - Csheterocycloalkyl ring optionally containing an additional heteroatom selected from N, O and S;
  • each R 13 is independently selected from halogen, -CN, -LR 9 , -LOR 9 , -OLR 9 , -LR 10 , -LOR 10 , -OLR 10 , -LR 8 , -LOR 8 , -OLR 8 , -LSR 8 ,
  • each R A is independently selected from -R 8 , -R 7 , -OR 7 , -OR 8 , -R 10 ,
  • n is, independently at each occurrence, 0, 1, 2, 3, 4, 5, 6, 7 or 8;
  • each m is independently selected from 1, 2, 3, 4, 5 and 6, and
  • t is 1, 2, 3, 4, 5, 6, 7 or 8; or (c) a pharmaceutically acceptable salt of any of (a) or (b).
  • benzonaphthyridine compounds are described in WO 2009/111337.
  • a benzonaphthyridine compound, or a salt thereof, can be used on its own, or in combination with one or more further compounds.
  • a benzonaphthyridine compound can be used in combination with an oil-in-water emulsion or a mineral-containing composition.
  • a benzonaphthyridine compound is used in combination with an oil- in-water emulsion (e.g. a squalene-water emulsion, such as MF59) or a mineral-containing composition (e.g., a mineral said such as an aluminum salt or a calcium salt).
  • an oil- in-water emulsion e.g. a squalene-water emulsion, such as MF59
  • a mineral-containing composition e.g., a mineral said such as an aluminum salt or a calcium salt.
  • a thiosemicarbazone compound such as those disclosed in reference 94. Methods of formulating, manufacturing, and screening for active compounds are also described in reference 94.
  • the thiosemicarbazones are particularly effective in the stimulation of human peripheral blood mononuclear cells for the production of cytokines, such as TNF-a.
  • a tryptanthrin compound such as those disclosed in reference 95. Methods of formulating, manufacturing, and screening for active compounds are also described in reference 95.
  • the thiosemicarbazones are particularly effective in the stimulation of human peripheral blood mononuclear cells for the production of cytokines, such as TNF-a.
  • a nucleoside analog such as: (a) Isatorabine (ANA-245; 7-thia-8-oxoguanosine): and prodrugs thereof; (b) ANA975; (c) ANA-025-1; (d) ANA380; (e) the compounds disclosed in references 96 to 98; (f) a compound having the formula: wherein:
  • Ri and R 2 are each independently H, halo, -NR a Rb, -OH, Ci_6 alkoxy, substituted Ci_6 alkoxy, heterocyclyl, substituted heterocyclyl, C 6 -io aryl, substituted C 6 -io aryl, Ci_6 alkyl, or substituted Ci_6 alkyl;
  • R 3 is absent, H, Ci_ 6 alkyl, substituted Ci_ 6 alkyl, C 6 -io aryl, substituted C 6 -io aryl, heterocyclyl, or substituted heterocyclyl;
  • R 4 and R5 are each independently H, halo, heterocyclyl, substituted heterocyclyl, -C(0)-Rd, Ci_6 alkyl, substituted Ci_6 alkyl, or bound together to form a 5 membered ring as in R 4 _s:
  • R 4 -5 the binding being achieved at the bonds indicated by a Xi and X 2 are each independently N, C, O, or S;
  • R 8 is H, halo, -OH, Ci_ 6 alkyl, C 2 _ 6 alkenyl, C 2 _ 6 alkynyl, -OH, -NR a R b , - (CH 2 ) n -0-R c , -0-(d_ 6 alkyl), -S(0) p R e , or -C(0)-R d ;
  • R9 is H, Ci-6 alkyl, substituted Ci_6 alkyl, heterocyclyl, substituted heterocyclyl or R 3 ⁇ 4 , wherein Rg a is:
  • Rio and Rn are each independently H, halo, Ci_6 alkoxy, substituted Ci_6 alkoxy, -NR a R b , or -OH; each R a and R b is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, -C(0)Ra, C6-10 aryl;
  • each R c is independently H, phosphate, diphosphate, triphosphate, Ci_6 alkyl, or substituted Ci_6 alkyl;
  • each R d is independently H, halo, Ci_6 alkyl, substituted Ci_6 alkyl, Ci_6 alkoxy, substituted Ci_6 alkoxy, -NH 2 , -NH(Ci_6 alkyl), -NH(substituted Ci_6 alkyl), - N(Ci_6 alkyl) 2 , -N(substituted Ci_6 alkyl) 2 , C 6 -io aryl, or heterocyclyl;
  • each R e is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, C 6 -io aryl, substituted C 6 -io aryl, heterocyclyl, or substituted heterocyclyl;
  • each Rf is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, -C(0)R d , phosphate, diphosphate, or triphosphate;
  • each n is independently 0, 1 , 2, or 3 ;
  • each p is independently 0, 1 , or 2; or
  • Compounds disclosed in reference 100 including: Acylpiperazine compounds, Indoledione compounds, Tetrahydraisoquinoline (THIQ) compounds, Benzocyclodione compounds, Aminoazavinyl compounds, Aminobenzimidazole quinolinone (ABIQ) compounds (101 , 102), Hydrapthalamide compounds, Benzophenone compounds, Isoxazole compounds, Sterol compounds, Quinazilinone compounds, Pyrrole compounds (103), Anthraquinone compounds, Quinoxaline compounds, Triazine compounds, Pyrazalopyrimidine compounds, and Benzazole compounds (104).
  • aminoalkyl glucosaminide phosphate derivative such as RC-529 (106, 107).
  • a phosphazene such as poly[di(carboxylatophenoxy)phosphazene] ("PCPP") as described, for example, in references 108 and 109.
  • PCPP poly[di(carboxylatophenoxy)phosphazene]
  • SIPs Small molecule immunopotentiators
  • the cytokine-inducing agents for use in the present invention may be modulators and/or agonists of Toll-Like Receptors (TLR).
  • TLR Toll-Like Receptors
  • they may be agonists of one or more of the human TLR1, TLR2, TLR3, TLR4, TLR7, TLR8, and/or TLR9 proteins.
  • Preferred agents are agonists of TLR4 (e.g.
  • modified natural lipid As derived from enterobacterial lipopolysaccharides, phospholipid compounds, such as the synthetic phospholipid dimer, E6020), TLR7 (e.g., benzonaphthyridines, imidazoquinolines) and/or TLR9 (e.g., CpG oligonucleotides). These agents are useful for activating innate immunity pathways.
  • phospholipid compounds such as the synthetic phospholipid dimer, E6020
  • TLR7 e.g., benzonaphthyridines, imidazoquinolines
  • TLR9 e.g., CpG oligonucleotides
  • the cytokine-inducing agent can be added to the composition at various stages during its production. For example, it may be within an antigen composition, and this mixture can then be added to an oil-in- water emulsion. As an alternative, it may be within an oil-in-water emulsion, in which case the agent can either be added to the emulsion components before emulsification, or it can be added to the emulsion after emulsification. Similarly, the agent may be coacervated within the emulsion droplets.
  • the location and distribution of the cytokine-inducing agent within the final composition will depend on its hydrophilic/lipophilic properties, e.g., the agent can be located in the aqueous phase, in the oil phase, and/or at the oil- water interface.
  • the cytokine-inducing agent can be conjugated to a separate agent, such as an antigen (e.g., CRM197).
  • a separate agent such as an antigen (e.g., CRM197).
  • an antigen e.g., CRM197
  • the adjuvants may be non-covalently associated with additional agents, such as by way of hydrophobic or ionic interactions.
  • Preferred cytokine-inducing agents are (a) benzonapthridine compounds; (b) immunostimulatory oligonucleotides and (c) 3dMPL.
  • Immunostimulatory oligonucleotides can include nucleotide
  • a CpG sequence may be directed to TLR9, such as the motif GTCGTT or TTCGTT (120).
  • the CpG sequence may be specific for inducing a Thl immune response, such as a CpG- A ODN
  • CpG-A and CpG-B ODNs are discussed in refs. 121-123.
  • the CpG is a CpG- A ODN.
  • the CpG oligonucleotide is constructed so that the 5' end is accessible for receptor recognition.
  • two CpG oligonucleotide sequences may be attached at their 3' ends to form "immunomers". See, for example, references 120 & 124- 126.
  • a useful CpG adjuvant is CpG7909, also known as PROMUNE (TM) (Coley
  • TpG sequences can be used (127). These oligonucleotides may be free from unmethylated CpG motifs.
  • the immunostimulatory oligonucleotide may be pyrimidine-rich.
  • it may comprise more than one consecutive thymidine nucleotide (e.g., TTTT, as disclosed in ref. 127), and/or it may have a nucleotide composition with >25 thymidine (e.g., >35 , >40 , >50 , >60 , >80 , etc.).
  • it may comprise more than one consecutive cytosine nucleotide (e.g., CCCC, as disclosed in ref.
  • oligonucleotides may be free from unmethylated CpG motifs.
  • Immunostimulatory oligonucleotides will typically comprise at least 20 nucleotides. They may comprise fewer than 100 nucleotides.
  • 3dMPL also known as 3 de-O-acylated monophosphoryl lipid A or
  • 3dMPL is an adjuvant in which position 3 of the reducing end glucosamine in monophosphoryl lipid A has been de-acylated.
  • 3dMPL has been prepared from a heptoseless mutant of Salmonella minnesota, and is chemically similar to lipid A but lacks an acid-labile phosphoryl group and a base-labile acyl group. It activates cells of the monocyte/macrophage lineage and stimulates release of several cytokines, including IL-1, IL-12, TNF-a and GM-CSF (see also ref. 128). Preparation of 3dMPL was originally described in reference 129.
  • 3dMPL can take the form of a mixture of related molecules, varying by their acylation (e.g., having 3, 4, 5 or 6 acyl chains, which may be of different lengths).
  • the two glucosamine (also known as 2-deoxy-2-amino-glucose) monosaccharides are N-acylated at their 2-position carbons (i.e., at positions 2 and 2'), and there is also O-acylation at the 3' position.
  • the group attached to carbon 2 has formula -NH-CO-CH 2 -CR 1 R 1 .
  • the group attached to carbon 2' has formula -NH-CO-CH 2 -CR 2 R 2' .
  • the group attached to carbon 3' has formula -0-CO-CH 2 -CR 3 R 3 .
  • a representative structure is:
  • Groups R 1 , R 2 and R 3 are each independently -(CH 2 ) n -CH 3 .
  • the value of n is preferably between 8 and 16, more preferably between 9 and 12, and is most preferably 10.
  • Groups R 1 , R 2' and R 3' can each independently be: (a) -H; (b) -OH; or (c) - 0-CO-R 4 ,where R 4 is either -H or -(CH 2 ) m -CH 3 , wherein the value of m is preferably between 8 and 16, and is more preferably 10, 12 or 14. At the 2 position, m is preferably 14. At the 2' position, m is preferably 10. At the 3' position, m is preferably 12.
  • Groups R 1 , R 2 and R 3 are thus preferably -O-acyl groups from dodecanoic acid, tetradecanoic acid or hexadecanoic acid.
  • the 3dMPL has only 3 acyl chains (one on each of positions 2, 2' and 3') ⁇
  • the 3dMPL can have 4 acyl chains.
  • the 3dMPL can have 5 acyl chains.
  • the 3dMPL can have 6 acyl chains.
  • the 3dMPL adjuvant used according to the invention can be a mixture of these forms, with from 3 to 6 acyl chains, but it is preferred to include 3dMPL with 6 acyl chains in the mixture, and in particular to ensure that the hexaacyl chain form makes up at least 10% by weight of the total 3dMPL e.g., >20%, >30%, >40%, >50% or more. 3dMPL with 6 acyl chains has been found to be the most adjuvant-active form.
  • references to amounts or concentrations of 3dMPL in compositions of the invention refer to the combined 3dMPL species in the mixture.
  • 3dMPL can form micellar aggregates or particles with different sizes e.g., with a diameter ⁇ 150nm or >500nm. Either or both of these can be used with the invention, and the better particles can be selected by routine assay. Smaller particles ⁇ e.g., small enough to give a clear aqueous suspension of 3dMPL) are preferred for use according to the invention because of their superior activity (130). Preferred particles have a mean diameter less than 220nm, more preferably less than 200nm or less than 150nm or less than 120nm, and can even have a mean diameter less than lOOnm. In most cases, however, the mean diameter will not be lower than 50nm.
  • Particle diameter can be assessed by the routine technique of dynamic light scattering, which reveals a mean particle diameter. Where a particle is said to have a diameter of x nm, there will generally be a distribution of particles about this mean, but at least 50% by number (e.g., >60%, >70%, >80%, >90%, or more) of the particles will have a diameter within the range x+25%.
  • 3dMPL can advantageously be used in combination with an oil-in-water emulsion. Substantially all of the 3dMPL may be located in the aqueous phase of the emulsion.
  • the 3dMPL can be used on its own, or in combination with one or more further compounds. For example, it is known to use 3dMPL in combination with the QS21 saponin (131) (including in an oil-in- water emulsion (132)), with an immunostimulatory oligonucleotide, with both QS21 and an immunostimulatory oligonucleotide, with aluminum phosphate (133), with aluminum hydroxide (134), or with both aluminum phosphate and aluminum hydroxide.
  • Fatty adjuvants that can be used with the invention include the oil-in-water emulsions described above, and also include, for example:
  • ER804057 is also called E6020.
  • a phospholipid compound of formula I, II or III, or a salt thereof can be used on its own, or in combination with one or more further compounds.
  • a compound of formula I, II or III can be used in combination with an oil-in-water emulsion or a mineral-containing composition.
  • E6020 is used in combination with an oil-in- water emulsion (e.g. a squalene-water emulsion, such as MF59) or a mineral-containing composition (e.g., a mineral said such as an aluminum salt or a calcium salt).
  • a formulation of a cationic lipid and a (usually neutral) co-lipid such as
  • Lipopeptides i.e., compounds comprising one or more fatty acid residues and two or more amino acid residues
  • lipopeptides based on glycerylcysteine include compounds of the following formula in which each of R 1 and R 2 represents a saturated or unsaturated, aliphatic or mixed aliphatic - cycloaliphatic hydrocarbon radical having from 8 to 30, preferably 11 to 21, carbon atoms that is optionally also substituted by oxygen functions
  • R 3 represents hydrogen or the radical R1-CO-O-CH2- in which R 1 has the same meaning as above
  • X represents an amino acid bonded by a peptide linkage and having a free, esterified or amidated carboxy group, or an amino acid sequence of from 2 to 10 amino acids of which the terminal carboxy group is in free, esterified or amidated form.
  • the amino acid sequence comprises a D-amino acid, for example, D-glutamic acid (D-Glu) or
  • TLR2 Bacterial lipopeptides generally recognize TLR2, without requiring TLR6 to participate.
  • TLRs operate cooperatively to provide specific recognition of various triggers, and TLR2 plus TLR6 together recognize peptidoglycans, while TLR2 recognizes lipopeptides without TLR6.
  • TLR2 recognizes lipopeptides without TLR6.
  • Synthetic lipopeptides tend to behave similarly, and are primarily recognized by TLR2.
  • Lipopeptides suitable for use as adjuvants include compounds have the formula:
  • each R la and R lb is independently an aliphatic or cycloaliphatic-aliphatic hydrocarbon group having 7-21 carbon atoms, optionally substituted by oxygen functions, or one of R la and R lb , but not both, is H;
  • R 2 is an aliphatic or cycloaliphatic hydrocarbon group having 1-21 carbon atoms and
  • n 0 or 1 ;
  • As 1 is a D- or L-alpha-amino acid
  • Z 1 and Z 2 each independently represent -OH or the N-terminal radical of a D- or L- alpha amino acid of an amino-(lower alkane)-sulfonic acid or of a peptide having up to 6 amino acids selected from the D- and L-alpha aminocarboxylic acids and amino-lower alkyl-sulfonic acids; and
  • Z 3 is H or -CO-Z 4 , wher Z 4 is -OH or the N-terminal radical of a D- or L-alpha amino acid of an amino-(lower alkane)- sulfonic acid or of a peptide having up to 6 amino acids selected from the D and L-alpha aminocarboxylic acids and amino-lower alkyl-sulfonic acids; or an ester or amide formed from the carboxylic acid of such compounds.
  • Suitable amides include -N3 ⁇ 4 and NH(lower alkyl)
  • suitable esters include C1-C4 alkyl esters, (lower alkyl or lower alkane, as used herein, refers to Ci-C 6 straight chain or branched alkyls).
  • the lipopeptide has the formula: [0199] Another example of a lipopeptide species is called LP40, and is an agonist of TLR2. Akdis, et al., Eur. J. Immunology, 33: 2717-26 (2003).
  • murein lipoproteins are related to a known class of lipopeptides from E. coli, referred to as murein lipoproteins. Certain partial degradation products of those proteins called murein lipopetides are described in Hantke, et al., Eur. J. Biochem. , 34: 284-296 (1973). These comprise a peptide linked to N-acetyl muramic acid and are thus related to Muramyl peptides, which are described in Baschang, et al., Tetrahedron, 45(20): 6331-6360 (1989).
  • the adjuvants known as "aluminum hydroxide” and “aluminum phosphate” may be used. These names are conventional, but are used for convenience only, as neither is a precise description of the actual chemical compound which is present (e.g., see chapter 9 of reference 74).
  • the invention can use any of the "hydroxide” or "phosphate” adjuvants that are in general use as adjuvants.
  • the adjuvants known as "aluminum hydroxide” are typically aluminum oxyhydroxide salts, which are usually at least partially crystalline.
  • Aluminum oxyhydroxide which can be represented by the formula AIO(OH)
  • IR infrared
  • IR infrared
  • the de gree of crystallinity of an aluminum hydroxide adjuvant is reflected by the width of the diffraction band at half height (WHH), with poorly-crystalline particles showing greater line broadening due to smaller crystallite sizes.
  • the surface area increases as WHH increases, and adjuvants with higher WHH values have been seen to have greater capacity for antigen adsorption.
  • a fibrous morphology e.g., as seen in transmission electron micrographs
  • the pi of aluminum hydroxide adjuvants is typically about ⁇ ⁇ , i.e., the adjuvant itself has a positive surface charge at physiological pH.
  • Adsorptive capacities of between 1.8-2.6 mg protein per mg Al +++ at pH 7.4 have been reported for aluminum hydroxide adjuvants.
  • the adjuvants known as "aluminum phosphate” are typically aluminum hydroxyphosphates, often also containing a small amount of sulfate (i.e., aluminum hydroxyphosphate sulfate). They may be obtained by precipitation, and the reaction conditions and concentrations during precipitation influence the degree of substitution of phosphate for hydroxyl in the salt. Hydroxyphosphates generally have a PO 4 /AI molar ratio between 0.3 and 1.2. Hydroxyphosphates can be distinguished from strict A1P0 4 by the presence of hydroxyl groups. For example, an IR spectrum band at 3164cm "1 (e.g., when heated to 200°C) indicates the presence of structural hydroxyls (ch.9 of ref. 74)
  • the PO 4 /AI 3"1" molar ratio of an aluminum phosphate adjuvant will generally be between 0.3 and 1.2, preferably between 0.8 and 1.2, and more preferably 0.95+0.1.
  • the aluminum phosphate will generally be amorphous, particularly for hydroxyphosphate salts.
  • a typical adjuvant is amorphous aluminum hydroxyphosphate with PO 4 /AI molar ratio between 0.84 and 0.92, included at 0.6mg Al 3+ /ml.
  • the aluminum phosphate will generally be particulate (e.g., plate-like morphology as seen in transmission electron micrographs). Typical diameters of the particles are in the range 0.5-20 ⁇ (e.g., about 5-10 ⁇ ) after any antigen adsorption.
  • Adsorptive capacities of between 0.7-1.5 mg protein per mg Al +++ at pH 7.4 have been reported for aluminum phosphate adjuvants.
  • Aluminum phosphates used according to the invention will generally have a PZC of between 4.0 and 7.0, more preferably between 5.0 and 6.5, e.g., about 5.7.
  • Suspensions of aluminum salts used to prepare compositions of the invention may contain a buffer (e.g., a phosphate or a histidine or a Tris buffer), but this is not always necessary.
  • the suspensions are preferably sterile and pyrogen-free.
  • a suspension may include free aqueous phosphate ions e.g., present at a concentration between 1.0 and 20 mM, preferably between 5 and 15 mM, and more preferably about 10 mM.
  • the suspensions may also comprise sodium chloride.
  • the invention can use a mixture of both an aluminum hydroxide and an aluminum phosphate.
  • there may be more aluminum phosphate than hydroxide e.g., a weight ratio of at least 2: 1 e.g., >5: 1, >6: 1, >7: 1 , >8: 1, >9: 1, etc.
  • the concentration of Al +++ in a composition for administration to a patient is preferably less than lOmg/ml e.g., ⁇ 5 mg/ml, ⁇ 4 mg/ml, ⁇ 3 mg/ml, ⁇ 2 mg/ml, ⁇ 1 mg/ml, etc.
  • a preferred range is between 0.3 and lmg/ml.
  • a maximum of 0.85mg/dose is preferred.
  • the adjuvant component may include one or more further adjuvant or immunostimulating agents.
  • additional components include, but are not limited to: a benzonaphthyridine compound, a 3- O-deacylated monophosphoryl lipid A adjuvant ('3d-MPL'); and/or an oil-in-water emulsion.
  • 3d-MPL has also been referred to as 3 de-O-acylated monophosphoryl lipid A or as
  • 3-0-desacyl-4'-monophosphoryl lipid A The name indicates that position 3 of the reducing end glucosamine in monophosphoryl lipid A is de-acylated. It has been prepared from a heptoseless mutant of S.minnesota, and is chemically similar to lipid A but lacks an acid- labile phosphoryl group and a base-labile acyl group. It activates cells of the
  • IL-1 monocyte/macrophage lineage and stimulates release of several cytokines, including IL-1 , IL- 12, TNF-a and GM-CSF.
  • cytokines including IL-1 , IL- 12, TNF-a and GM-CSF.
  • MPL Corixa Corporation
  • an aluminum hydroxide and/or aluminum phosphate adjuvant is useful, particularly in children, and antigens are generally adsorbed to these salts. Squalene- in- water emulsions are also preferred, particularly in the elderly. Useful adjuvant
  • combinations include combinations of Thl and Th2 adjuvants such as CpG and alum, or resiquimod and alum.
  • a combination of aluminum phosphate and 3dMPL may be used.
  • Other combinations that may be used include: alum and a benzonapthridine compound or a SMIP, a squalene-in-water emulsion (such as MF59) and a benzonapthridine compound or a SMIP, and E6020 and a squalene-in-water emulsion, such as MF59) or alum.
  • compositions of the invention may elicit both a cell mediated immune response as well as a humoral immune response.
  • CD8 T cells Two types of T cells, CD4 and CD8 cells, are generally thought necessary to initiate and/or enhance cell mediated immunity and humoral immunity.
  • CD8 T cells can express a CD8 co-receptor and are commonly referred to as Cytotoxic T lymphocytes (CTLs).
  • CTLs Cytotoxic T lymphocytes
  • CD8 T cells are able to recognized or interact with antigens displayed on MHC Class I molecules.
  • CD4 T cells can express a CD4 co-receptor and are commonly referred to as T helper cells.
  • CD4 T cells are able to recognize antigenic peptides bound to MHC class II molecules.
  • the CD4 cells Upon interaction with a MHC class II molecule, the CD4 cells can secrete factors such as cytokines. These secreted cytokines can activate B cells, cytotoxic T cells, macrophages, and other cells that participate in an immune response.
  • Helper T cells or CD4+ cells can be further divided into two functionally distinct subsets: TH1 phenotype and TH2 phenotypes which differ in their cytokine and effector function.
  • Activated TH1 cells enhance cellular immunity (including an increase in antigen-specific CTL production) and are therefore of particular value in responding to intracellular infections.
  • Activated TH1 cells may secrete one or more of IL-2, IFN- ⁇ , and TNF- ⁇ .
  • a TH1 immune response may result in local inflammatory reactions by activating macrophages, NK (natural killer) cells, and CD8 cytotoxic T cells (CTLs).
  • a TH1 immune response may also act to expand the immune response by stimulating growth of B and T cells with IL-12.
  • TH1 stimulated B cells may secrete IgG2a.
  • Activated TH2 cells enhance antibody production and are therefore of value in responding to extracellular infections.
  • Activated TH2 cells may secrete one or more of IL-4, IL-5, IL-6, and IL-10.
  • a TH2 immune response may result in the production of IgGl , IgE, IgA and memory B cells for future protection.
  • An enhanced immune response may include one or more of an enhanced TH1 immune response and a TH2 immune response.
  • a TH1 immune response may include one or more of an increase in CTLs, an increase in one or more of the cytokines associated with a TH1 immune response (such as IL- 2, IFN- ⁇ , and TNF- ⁇ ), an increase in activated macrophages, an increase in NK activity, or an increase in the production of IgG2a.
  • the enhanced TH1 immune response will include an increase in IgG2a production.
  • a TH1 immune response may be elicited using a TH1 adjuvant.
  • a TH1 adjuvant will generally elicit increased levels of IgG2a production relative to immunization of the antigen without adjuvant.
  • TH1 adjuvants suitable for use in the invention may include for example saponin formulations, virosomes and virus like particles, non-toxic derivatives of enterobacterial lipopoly saccharide (LPS), immunostimulatory oligonucleotides.
  • Immunostimulatory oligonucleotides such as oligonucleotides containing a CpG motif, are preferred TH1 adjuvants for use in the invention.
  • a TH2 immune response may include one or more of an increase in one or more of the cytokines associated with a TH2 immune response (such as IL-4, IL-5, IL-6 and IL-10), or an increase in the production of IgGl , IgE, IgA and memory B cells.
  • the enhanced TH2 immune response will include an increase in IgGl production.
  • a TH2 immune response may be elicited using a TH2 adjuvant.
  • a TH2 adjuvant will generally elicit increased levels of IgGl production relative to immunization of the antigen without adjuvant.
  • TH2 adjuvants suitable for use in the invention include, for example, mineral containing compositions, oil-emulsions, and ADP-ribosylating toxins and detoxified derivatives thereof. Mineral containing compositions, such as aluminium salts are preferred TH2 adjuvants for use in the invention.
  • a composition may include a combination of a THl adjuvant and a TH2 adjuvant.
  • a composition elicits an enhanced THl and an enhanced TH2 response, i.e., an increase in the production of both IgGl and IgG2a production relative to immunization without an adjuvant.
  • the composition comprising a combination of a THl and a TH2 adjuvant elicits an increased THl and/or an increased TH2 immune response relative to immunization with a single adjuvant (i.e., relative to immunization with a THl adjuvant alone or immunization with a TH2 adjuvant alone).
  • the immune response may be one or both of a THl immune response and a TH2 response.
  • immune response provides for one or both of an enhanced THl response and an enhanced TH2 response.
  • the enhanced immune response may be one or both of a systemic and a mucosal immune response.
  • the immune response provides for one or both of an enhanced systemic and an enhanced mucosal immune response.
  • the mucosal immune response is a TH2 immune response.
  • the mucosal immune response includes an increase in the production of IgA.
  • compositions of the invention are suitable for administration to mammals, and the invention provides a method of inducing an immune response in a mammal, comprising the step of administering a composition (e.g., an immunogenic composition) of the invention to the mammal.
  • a composition e.g., an immunogenic composition
  • the compositions can be used to produce a vaccine formulation for immunizing a mammal.
  • the mammal is typically a human, and the RSV F protein is typically a human RSV F protein.
  • the mammal can be any other mammal that is susceptible to infection with RSV, such as a cow that can be infected with bovine RSV.
  • the immune response may be raised following administration of a purified RSV F protein, an alphavirus particle, or self-replicating RNA.
  • the invention also provides the use of two or more pre-fusion chimerid proteins based on two or more different non-RSV (e.g., parainfluenza virus,
  • metapneumovirus F pre-fusion proteins i.e., PIV5 and NDV
  • inoculation with one chimeric pre-fusion F, and a second inoculation with the second pre-fusion F may prime several antibodies, some to RSV and some to the template protein backbone.
  • the second inoculation may bias boosting of only the shared RSV F neutralizing epitopes.
  • the invention also provides a composition of the invention for use as a medicament, e.g., for use in immunizing a patient against RSV infection.
  • the invention also provides the use of a polypeptide as described above in the manufacture of a medicament for raising an immune response in a patient.
  • the immune response raised by these methods and uses will generally include an antibody response, preferably a protective antibody response.
  • Methods for assessing antibody responses after RSV vaccination are well known in the art.
  • compositions of the invention can be administered in a number of suitable ways, such as intramuscular injection (e.g., into the arm or leg), subcutaneous injection, intranasal administration, oral administration, intradermal administration, transcutaneous administration, transdermal administration, and the like.
  • intramuscular injection e.g., into the arm or leg
  • subcutaneous injection intranasal administration
  • oral administration intradermal administration
  • transcutaneous administration transdermal administration
  • compositions of the invention can be administered in a number of suitable ways, such as intramuscular injection (e.g., into the arm or leg), subcutaneous injection, intranasal administration, oral administration, intradermal administration, transcutaneous administration, transdermal administration, and the like.
  • the appropriate route of administration will be dependent upon the age, health and other characteristics of the mammal. A clinician will be able to determine an appropriate route of administration based on these and other factors.
  • Immunogenic compositions, and vaccine formulations may be used to treat both children and adults, including pregnant women.
  • a subject may be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old, or at least 55 years old.
  • Preferred subjects for receiving the vaccines are the elderly (e.g., >50 years old, >60 years old, and preferably >65 years), the young (e.g., ⁇ 6 years old, such as 4 - 6 years old, ⁇ 5 years old), and pregnant women.
  • the vaccines are not suitable solely for these groups, however, and may be used more generally in a population.
  • Treatment can be by a single dose schedule or a multiple dose schedule. Multiple doses may be used in a primary immunization schedule and/or in a booster immunization schedule. In a multiple dose schedule the various doses may be given by the same or different routes, e.g., a parenteral prime and mucosal boost, a mucosal prime and parenteral boost, etc. Administration of more than one dose (typically two doses) is particularly useful in immunologically naive patients. Multiple doses will typically be administered at least 1 week apart (e.g., about 2 weeks, about 3 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 16 weeks, and the like.).
  • Vaccine formulations produced using a composition of the invention may be administered to patients at substantially the same time as (e.g., during the same medical consultation or visit to a healthcare professional or vaccination centre) other vaccines.
  • composition “comprising” encompasses “including” as well as “consisting” and “consisting essentially of” e.g., a composition “comprising” X may consist exclusively of X or may include something additional e.g., X + Y.
  • a process comprising a step of mixing two or more components does not require any specific order of mixing.
  • components can be mixed in any order. Where there are three components then two components can be combined with each other, and then the combination may be combined with the third component, etc.
  • animal (and particularly bovine) materials are used in the culture of cells, they should be obtained from sources that are free from transmissible spongiform encaphalopathies (TSEs), and in particular free from bovine spongiform encephalopathy (BSE). Overall, it is preferred to culture cells in the total absence of animal-derived materials.
  • TSEs transmissible spongiform encaphalopathies
  • BSE bovine spongiform encephalopathy
  • a cell substrate is used for reassortment or reverse genetics procedures, it is preferably one that has been approved for use in human vaccine production e.g., as in Ph Eur general chapter 5.2.3.
  • a stable, non-aggregating soluble RSV F subunit antigen was prepared by deletion of the fusion peptide, transmembrane region, and cytoplasmic domain (FIG. 1). This engineered F was expressed efficiently and was readily purified. Electron microscopy of negatively stained specimens showed that it formed non-aggregated, homogeneous crutch- shaped molecules, consistent with post-fusion F trimers (FIG. 2A). This engineered F trimer was stable, and circular dichroism spectroscopy revealed no significant melting at temperatures up to 95°C (FIGS. 2B and 2C).
  • This RSV F protein was crystallized and its structure was determined by molecular replacement and three-fold non-crystallographic symmetry (NCS) averaging (Table 3 and FIG. 3). The structure does not include the p27 fragment (the peptide between the two furin sites that is lost upon cleavage), the fusion peptide, the transmembrane region, or the cytoplasmic domain (FIG. 4).
  • NCS non-crystallographic symmetry
  • the overall architecture of post- fusion RSV F is shared with other post-fusion parainfluenza fusion proteins.
  • the protein is composed of three tightly intertwined subunits, forming a globular head and an elongated stalk. Each subunit contains three domains, designated I, II, and III (FIGS. 4A-C). Domains I and II are at the top of the trimeric head and form a triangular crown. Domain III forms the base of the head. A long helix, HRA, extends from domain III and forms the trimeric coiled-coil in the center of the stalk.
  • the HRB helix is tethered to domain II and reaches down to the head-distal end of the stalk, where it forms the outer coils of a six-helix bundle with the HRA interior coiled-coil.
  • the hydrophobic fusion peptide (N-terminal to HRA) and the transmembrane region (C-terminal to HRB) would be juxtaposed at the bottom of the stalk and inserted into the target cell membrane.
  • Domains I and II of RSV, parainfluenza virus 3 (PIV3), and parainfluenza virus 5 (PIV5) F proteins are structurally conserved (FIGS. 5A and 5B). The only significant difference is in the orientation of the sole helix of domain I ( ⁇ 3 of RSV F and ot6 of PIV3 and PIV5 Fs) relative to their common ⁇ -sheets. In contrast, RSV F domain III has features that were not predicted from parainfluenza-based modeling (FIG. 6). When the four-stranded ⁇ -sheets of RSV F domain III and PIV3 F domain III are superimposed, key differences in the domains' helical regions are apparent.
  • Helix HRA kinks at a more N-terminal position in RSV F than in PIV3 F, causing an approximately 60° difference in the rotation of the heads relative to the stalks (FIGS. 6A, 6B, 6D).
  • Influenza hemagglutinins also vary in the orientations of their heads relative to their stalks, with 30°-50° differences in rotation between subtypes. (Ha, Y. et al., Embo Journal 21, 865-875 (2002)).
  • the RSV F domain III helical bundle region contains an extra helix (ot6), changing the orientation of the bundled helices relative to those in parainfluenza Fs (FIGS. 6A-C and FIG. 1).
  • RSV F helices ot5 and ot6 are almost parallel and are exposed on the trimer surface; the equivalent to RSV F ot6 helix in the PIV3 helical bundle (ot5, FIG. 6C) is buried in the inter-subunit interface of the trimer.
  • RSV F helices ot5 and ot6 form the epitope bound by the related neutralizing antibodies Palivizumab and Motavizumab.
  • Pre-fusion and post-fusion parainfluenza F structures reveal en bloc shifts of domains and large rearrangements of HRA and HRB.
  • domain III of the pre-fusion PIV5 F structure the only reported pre-fusion parainfluenza F structure
  • the resulting pre-fusion RSV F model reveals a feature not apparent from modeling pre-fusion RSV F domains based on the PIV5 pre-fusion domain structures (McLellan, J. S. et al. Nat Struct Mol Biol 17, 248-250 (2010)).
  • Motavizumab epitope are exposed on the surface of the pre-fusion RSV F trimer, as they are on post-fusion RSV F trimer (FIG. 9).
  • the loop connecting ⁇ 4 and HRC (part of domain III) would hinder access of Palivizumab or
  • the loop may have sufficient flexibility to adopt an alternative conformation that permits antibody binding (FIG. 9B).
  • RSV F The antigenic structure of RSV F has been mapped by a variety of techniques (FIG. 1).
  • the best documented epitope clusters are designated A and C (Beeler, J. A. & van Wyke Coelingh, K. J Virol 63, 2941-2950 (1989)), and others have been proposed.
  • the Motavizumab-peptide structure corroborated the location of site A, although it called into question the site's exposure on the RSF F trimer (McLellan, J. S. et al. Structural basis of respiratory syncytial virus neutralization by motavizumab.
  • the PDB file of the RSV F pre-fusion model based on the RSV F post-fusion structure and sequence/domain alignments to the PIV5 pre-fusion structure.
  • the PDB file contains the atomic coordinates for the pre-fusion model, and can be used with suitable software for molecular visualization and analysis (e.g., Roger Sayle and E. James Milner- White. "RasMol: Biomolecular graphics for all", Trends in Biochemical Sciences (TIBS), September 1995, Vol. 20, No. 9, p. 374.) to display the model.
  • suitable software for molecular visualization and analysis e.g., Roger Sayle and E. James Milner- White. "RasMol: Biomolecular graphics for all", Trends in Biochemical Sciences (TIBS), September 1995, Vol. 20, No. 9, p. 374.
  • Included in the model are the three subunit chains with the fusion peptide and HRA region folded as in PIV5, making significant contacts with DHL HRB regions of the three subunits trim
  • An HRB deletion construct was designed to prevent formation of the post-fusion conformation. Two constructs have been designed to address this strategy. The first is a wild-type ectodomain lacking the HRB region (RSV F residues 1-483) call Del HRB:
  • the pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
  • the above sequence has both furin cleavage sites unaltered, and was expected to be processed by the cell.
  • the above sequence has the wild-type fusion peptide sequence.
  • the RSV F ectodomain-based proteins were cleaved by the cell and contained fusion peptides, they formed soluble aggregates with cellular debris in the form of RSV F rosettes. If this construct remained in the pre-fusion conformation (due to the lack of the HRB helix thought to be required for post-fusion conformation) than the fusion peptide should be burried in the RSV F head domain and should not form rosette aggreagates.
  • This construct was expressed, purified by affinity purification and evaluated by EM analysis (FIG. 12).
  • the pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
  • the RSV F model based on the RSV F post- fusion structure and PIV5 pre- fusion structure, was used to engineer cysteine mutations intended to form disulfide bonds that stabilize RSV F in the pre-fusion conformation (Figure 11).
  • the intrachain disulfide bond constructs were expressed, and were secreted from the cell into the media and then cleaved from F0 to F1/F2 to various degrees ( Figure 14).
  • RSV F T58C/V164C (expressed in mammalian cells) was found to express as a cleaved species which is secreted into the media.
  • the material was purified by chelating purification and evaluated by the rosette/trimer HPLC-SEC assay using the Bio-Sil 250 SEC column with 2x PBS as mobile phase ( Figure 15). As this is a cleaved F containing a fusion peptide, it was expected that would be in the postfusion form and would form rosettes and migrate in the void volume similar to postfusion RSV F rosettes ( Figure 15A). If the cleaved F protein harboring a fusion peptide was folded in the prefusion form, one would expect the fusion peptide to be buried in the prefusion head region preventing rosette formation.
  • Prefusion trimers should migrate in the included volume with a retention time similar to the RSV F postfusion trimer lacking the fusion peptide ( Figure 15B).
  • RSV F HRA Disulfide T58C V164C was run on HPLC-SEC, and the majority of material migrated in the column void volume, indicating the material was aggregating or forming rosettes of postfusion F.
  • the disulfide constructs were subsequently cloned into baculovirus expression vectors and three constructs (HRA disulfides N165C/V296C and K168C/V296C and HRB M396C/F483C) were expressed.
  • HRA disulfides N165C/V296C and K168C/V296C and HRB M396C/F483C were expressed.
  • K168C/V296C and M396C/F483C which were cleaved when expressed in mammalian cells, were secreted by insect cells predominantly as an uncleaved species (as shown by anti-HIS western blot). Both constructs migrated in the void fraction, which was inconsistent with previous observations that uncleaved species run as monomers.
  • the proteins may have aggregated by virtue of incorrect disulfide formation.
  • NDV F prefusion construct A strategy for rescuing the RSV HRA prefusion epitopes was developed to generate an NDV F prefusion construct and mutate select residues of the HRA to those of RSV F.
  • Initial attempts to replace the HRA of NDV with the HRA of RSV generated a construct which was not expressed/secreted from the cell. This indicated that the protein was misfolded. Further refinement of the residues of NDV F available for mutagenisis (i.e. those located on the protein surface) was required.
  • a new construct, NDV F stabilized with a GCN trimerization domain (uncleaved) migrated as a trimer by SEC analysis. This was expected as this construct was shown to be a pre-fusion trimer by electron microscopy (Swanson et al, 2010).
  • Electron micrographs of the NDV pre-fusion construct showed predominately the spherical heads expected for pre-fusion F (Figure 18D). A portion of the material seemed to be associated in rosette-like aggregates, which should not be permitted as the construct is uncleaved and pre-fusion. This amount of association may be due to aggregation by the HIS- tag, and may explain why the RSV Del-HRB Del-FP contained some aggregate/rosette even when the fusion peptide was not present. EM analysis of RSV F Del-HRB Del-FP showed that the material was heterogeneous (Figure 18E). RSV F Del-HRB Del-FP formed rosettelike structures similar to NDV F, as well as post-fusion like "crutches" and pre-fusion like "spheres”.
  • VDTVSVGNTLYYVNKQEGGGSAGSGHHHHHH** (SEQ ID NO:38)
  • a stable RSV prefusion F was generated by replacing the HRB region with either the HRB region of NDV (with or without an additional glycine linker: HRB2) or PIV5.
  • Mammalian expression of the non-native HRB constructs showed that each of the constructs were expressed and secreted well ( Figure 19). Additionally, the band observed migrated consistent with the cleaved Fl species, suggesting that the proteins were properly processed. The constructs existed with or without fusion peptide (as indicated in Figure 19).
  • Vaccine Adjuvants Preparation Methods and Research Protocols (Volume 42 of Methods in Molecular Medicine series). ISBN: 1-59259-083-7. Ed. O'Hagan.

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Abstract

The invention relates to pre-fusion RSV F protein and polypeptides that contain one or more amino acid mutations that stabilize the pre-fusion conformation or destabilize the post-fusion conformation. The invention also relates to methods for inducing an immune response to pre-fusion RSV F.

Description

PRE-FUSION RSV F ANTIGENS
RELATED APPLICATION
[001] This application claims priority to U.S. Provisional Application 61/486,005 filed on May 13, 2011. The entire contents of the foregoing application is incorporated herein by reference.
SEQUENCE LISTING
[002] The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 11, 2012, is named PAT05457.txt and is 98,385 bytes in size.
BACKGROUND OF THE INVENTION
[003] Respiratory syncytial virus (RSV) is an enveloped non-segmented negative- strand RNA virus in the family Paramyxoviridae, genus Pneumovirus. It is the most common cause of bronchiolitis and pneumonia among children in their first year of life. RSV also causes repeated infections including severe lower respiratory tract disease, which may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems.
[004] To infect a host cell, paramyxoviruses such as RSV, like other enveloped viruses such as influenza virus and HIV, require fusion of the viral membrane with a host cell's membrane. For RSV the conserved fusion protein (RSV F) fuses the viral and cellular membranes by coupling irreversible protein refolding with juxtaposition of the membranes. In current models, based on paramyxovirus studies, the RSV F protein initially folds into a "pre-fusion" conformation. During cell entry, the pre-fusion conformation undergoes refolding and conformational changes to its "post-fusion" conformation.
[005] The RSV F protein is translated from mRNA into an approximately 574 amino acid protein designated Fo. Post-translational processing of Fo includes removal of an N- terminal signal peptide by a signal peptidase in the endoplasmic reticulum. Fo is also cleaved at two sites (109/110 and 136/137) by cellular proteases (in particular furin) in the trans- Golgi. This cleavage results in the removal of a short intervening sequence and generates two subunits designated Fi (-50 kDa; C-terminal; approximately residues 137-574) and F2 (-20 kDa; N- terminal; approximately residues 1-109) that remain associated with each other. Fi contains a hydrophobic fusion peptide at its N-terminus and also two amphipathic heptad- repeat regions (HRA and HRB). HRA is near the fusion peptide and HRB is near the transmembrane domain. Three Fi-F2 heterodimers are assembled as homotrimers of Fi-F2 on the surface of the virion.
[006] A vaccine against RSV infection is not currently available, but is desired. Vaccine candidates based on the chief RSV neutralization antigen, the F glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the pre-fusion and post-fusion states. The magnitude of the rearrangement suggested that post-fusion F antigens would not efficiently elicit neutralizing antibodies, which presumably must bind epitopes exposed on the pre-fusion conformation. Accordingly, efforts to produce a vaccine against RSV have focused on developing subunit vaccines that contain pre-fusion forms of RSV F. (See, e.g., WO 2010/149745, WO 2010/149743, WO 2009/079796) This focus on pre-fusion forms of RSV F has been corroborated by available models of RSV F.
[007] Pre-fusion F is a "metastable" structure that readily rearranges into the lower energy post-fusion state, which then aggregates due to exposure of a hydrophobic fusion peptide (Begona Ruiz-Arguello, M. et al. Virology 298, 317-326 (2002) (142)). Large structural differences between the lollipop-shaped pre-fusion F trimer and the crutch-shaped post- fusion F trimer are apparent even at the resolution of electron microscopy of negatively stained specimens, suggesting that pre-fusion and post-fusion F may be antigenically distinct (Calder, L. J. et al. Virology 271, 122-131 (2000) (143)). To prevent viral entry, F-specific neutralizing antibodies presumably must bind the pre-fusion conformation of F on the virion, before the viral envelope fuses with a cellular membrane. However, efforts to generate a soluble, stabilized pre-fusion F subunit antigen have not yet yielded candidates suitable for testing in humans. Furthermore, analysis of a Motavizumab-peptide complex and homology modeling suggested that the dominant neutralizing epitope recognized by Palivizumab and Motavizumab might be buried in trimeric F, requiring at least a local dissociation for surface exposure to allow antibody binding (McLellan, J. S. et al. Nat Struct Mol Biol 17, 248-250 (2010)). There is a need for improved RSV F protein compositions and methods for making RSV F protein compositions. SUMMARY OF THE INVENTION
[008] The invention relates to pre-fusion respiratory syncytial virus (RSV) F polypeptides and pre-fusion chimeric F polypeptides.
[009] In some aspects, the pre-fusion respiratory syncytial virus (RSV) F polypeptide comprises at least two introduced cysteine residues that are in close proximity to one another, and form a disulfide bond that stabilizes the pre-fusion RSV F polypeptide. In particular embodiments, the HRB region contains an introduced cysteine residue and the DI and/or DII region contain an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residue in the HRB region and the introduced cysteine residue in the Dl or DII region. In other embodiments, the HRA region contains an introduced cysteine residue and the Dili region contains an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residue in the HRA region and the introduced cysteine residue in the III region. In other embodiments, the HRA region contains at least 2 introduced cysteine residues, and a disulfide bond is formed between the introduced cysteine residues in the HRA region.
[010] In other aspects, the pre-fusion respiratory syncytial virus (RSV) F polypeptide comprises a post-fusion modification selected from the group consisting of deletion of the HRA helix, deletion of the HRB helix, introduction of point mutations, addition of glycosylation sites and combinations thereof, wherein said post-fusion modification destabilizes the post-fusion conformation. In some embodiments, the destabilizing post-fusion modification is deletion of the HRB helix, in whole or in part. If desired, the destabilizing post-fusion modification can further comprise deletion of the fusion peptide, in whole or in part. In other embodiments, the destabilizing post-fusion modification includes addition of a glycosylation site, such as glycosylation on a residue selected from the group consisting of position 173, position 175 and position 184.
[011] In another aspect, the invention is a pre-fusion respiratory syncytial virus (RSV) F protein comprising three RSV F monomers, wherein at least two of the monomers contain an introduced cysteine residue, the introduced cysteine residues are in close proximity to one another and form a disulfide bond that stabilizes the pre-fusion RSV F protein.
[012] In another aspect, the invention is a chimeric pre-fusion F protein comprising a stabilized F protein from a virus other than RSV, such as parainfluenza virus F polypeptide or a metapneumovirus virus F polypeptide, that contains one or more neutralizing epitope of RSV F. Suitable neutralizing epitopes can be selected from the group consisting of the epitopes that are recognized by motavizumab, palivizumab, mAb 11, mAb 151 , mAb 1129, mAb 1153, mAb 1200, mAb 1214, mAb 1237, mAb 47F, mAb 7C2, mAb B4, Fab 19, mAb AK13A2, mAb 7.936, mAb 9.936, mAb 19, mAb 20, mAb 101F and combinations thereof.
[013] The invention relates to methods for inducing an anti -respiratory syncytial virus (RSV) immune response in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein. Preferably, the induced immune response is characterized by neutralizing antibodies to RSV and/or protective immunity against RSV.
[014] In particular aspects, the invention relates to a method for inducing or raising neutralizing anti-respiratory syncytial virus (RSV) F protein antibodies in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein.
[015] In particular aspects, the invention relates to a method for inducing or raising protective immunity against respiratory syncytial virus (RSV) in a subject, comprising administering to the subject an effective amount of an immunogenic composition comprising a pre-fusion RSV F protein or a pre-fusion chimeric F protein.
[016] In particular aspects, the invention relates to immunogenic compositions comprising a pre-fusion respiratory syncytial virus (RSV) F protein or a pre-fusion chimeric F protein.
[017] The pre-fusion RSV F protein that is used in the invention can be full length or truncated, such as a soluble ectodomain that lacks the cytoplasmic and transmembrane domains. The pre-fusion RSV F protein, e.g., full length or soluble ectodomain, may comprise functional furin cleavage sites at positions 109/110 and 136/137. In some preferred embodiments, that pre-fusion RSV F protein (e.g., full length or soluble ecto-domain) contains the amino acid sequence of the corresponding portion (e.g., ecto-domain) of a naturally occurring RSV F protein. In any of the aspects of the invention, the pre-fusion RSV F protein can be administered with or without an adjuvant as desired, and the immunogenic composition can comprise an adjuvant if desired.
BRIEF DESCRIPTION OF THE DRAWINGS [018] FIG. 1 shows a structure-based sequence alignment of four F proteins, secondary assignment, and key features. The alignment of RSV (SEQ ID NO:33), Newcastle disease virus (NDV) (SEQ ID NO:34), PIV3 (SEQ ID NO:36) and PIV5 (SEQ ID NO:35) Fs was generated with ClustalW2 (http://www.ebi.ac.uk/Tools/msa/clustalw2/), adjusted manually based on structural superposition using Lsqkab from the CCP4 suite of programs and displayed using ESPript version 2.2 (http://espript.ibcp.fr/ESPript ESPript ). Features of RSV F are indicated above the sequences; features of PIV3 F are indicated below the sequences. *CHO indicates RSV F glycosylation sites. Secondary structure elements are indicated, with arrows parallel to the sequences designating β-sheets, cylinders designating a- helices, "TT" designating turns, and coils designating 310 helices. The domain location of secondary structure symbols are indicated (DI, DII, Dili), except for RSV helices ot5 and ot6, which are labeled to indicate that they form the Motavizumab binding site and β20 and β21, which are labeled to indicate that they form the 10 IF binding site. Circled numbers (RSV) or triangled numbers (PIV3) designate residues that form disulfide bonds, with the same number for each partner in a disulfide-linked pair. The furin cleavage sites for RSV F and PIV3 F are indicated by vertical arrows labeled Fr. The RSV F p27 region released from the protein after furin cleavage is indicated by a black bar. The fusion peptides of RSV F and PIV3 F are labeled. The arrow in the fusion peptide indicates the first residue of the Fl fragment in the fusion peptide deletion construct used in this study. Residues that are identical in all four proteins are indicated by shaded boxes. Peptides used to investigate neutralizing binding sites are in open boxes and resistance mutations are indicated by asterisks.
[019] FIG. 2 shows electron microscopy and circular dichroism analysis of the RSV F post- fusion trimer. In FIG. 2A an electron micrograph of the RSV F protein shows a field of uniform crutch phenotypes consistent with the structure of post-fusion F proteins. FIG. 2B shows a CD melting curve of the post- fusion RSV F trimer observed at 210 nm, the observed spectral minimum of the folded RSV F protein. The CD absorption, y-axis, is plotted against temperature, x-axis. FIG. 2C shows a CD spectra of the post-fusion RSV F trimer at 20° and 95°C. The spectra were recorded from 320 to 190 nm and show at both temperatures characteristic helical minima for a folded protein.
[020] FIG. 3 shows representative electron densities of the crystallized RSV F protein. FIG. 3A is a side view of the original molecular replacement solution model, which contains the PIV3 post- fusion head in- frame with the 6-helix bundle of RSV F, shown in the initial electron density map (1σ) calculated after iterative real-space NCS three-fold averaging, histogram matching, and solvent flattening with phase extension from 7.0 to 3.2 A and no phase recombination. The head region fits poorly in the electron density. FIG. 3B Side view. The final model of RSV F shown in the averaged electron density map as described in FIG. 4A. FIG. 3C shows a top view of the RSV F protein structure shown in FIG. 4 A. FIG. 3D shows a top view of B. Model and electron density depicted as in FIG. 4B. FIG. 3E is a close up of a representative averaged electron density (gray) with the final model in stick representation. FIG. 3F shows the same view as in FIG. 4E but with final 2mFo-dFc electron density map contoured at 1.5 σ.
[021] FIG. 4 shows the RSV F ectodomain structure. 4A is a linear diagram. Listed residue numbers correspond to the N-terminus of each segment, the furin cleavage sites (arrow heads), and the C-terminus. DI-III, domains I-III; p27, excised peptide; FP, fusion peptide; HRA, B, and C, heptad repeats A, B, and C. 4B shows a ribbon representation of one subunit of the RSV F ectodomain trimer. Domains are labeled and shaded as in 4A, glycans are shown in black. 4C shows surface representation of the RSV F ectodomain trimer. The domains of one subunit are labeled and shaded as in 4A, the other two subunits are white and gray.
[022] FIG. 5 shows superposition of domains I and II of RSV F and PIV3 F. FIG. 5A shows a ribbon diagram of domain I from RSV and PIV3 superimposed by matching the common β-sheets. FIG 5B shows a ribbon diagram of domain II from RSV F and PIV3 F superimposed based on common β-strands. The secondary structure elements of RSV F are labeled.
[023] FIG. 6 illustrates a comparison between RSV and PIV3. FIG. 6 A is a ribbon diagram of RSV F domain III. FIG. 6B shows a ribbon diagram of the PIV3 domain III oriented to match orientation shown in FIG. 6A. FIG. 6C shows the detail of the RSV and PIV3 (which are shaded differently) domain III helical bundles superimposed based on domain III β-sheets. FIG. 6D shows RSV and PIV3 F ectodomain trimers (shaded as in A and B) superimposed based on their six-helix bundles. The image on the left shows a ribbon diagram viewed perpendicular to the three-fold axis; the image on the right is a surface representation viewed along the three-fold axis from the top of the head.
[024] FIG. 7 illustrates the Motavizumab epitope. FIG. 7A is a superposition of the Motavizumab-binding helices, ot5 and ot6, from the RSV F post-fusion trimer and the peptide-Motavizumab complex (PDB code 3ΓΧΤ). The post fusion trimer structure and the peptide-motavizumab complex structure are shaded differently. RSV residues bound by Motavizumab are shown in stick representation. Asterisks denote Palivizumab escape mutations. FIG. 7B shows a ribbon representation modeling a Motavizumab-RSV F post- fusion trimer complex. The VH and VL domains of the Fab are labeled; helices ot5 and ot6 from the RSV F structure and the peptide-Motavizumab structure are shaded differently; a glycan on RSV F is black; and the remainder of RSV F is white.
[025] FIG. 8 illustrates RSV F conformational changes, antigenic structure and Palivizumab binding. FIG. 8A is a surface representation of the post-fusion structure.
Antigenic sites A and C are outlined and labeled. Asterisks indicate residues selected in neutralization escape variants or forming contacts with an antibody in the determined structures of neutralizing antibody-peptide complexes. The HRA and HRB surfaces are shaded. FIG. 8B is a surface representation of a pre-fusion model, annotated as in A. FIG. 8C is a graph showing inhibition of Palivizumab binding to post-fusion RSV F by pooled sera from un-immunized mice or mice immunized with the RSV F antigen. Palivizumab binding (percentage of ELISA signal without competing sera) is plotted as a function of the dilution of competing pooled sera.
[026] FIG. 9 shows the exposure of the Motaviuzumab epitope in the post-fusion RSV F structure (A) and pre-fusion RSV F model (B). Fig. 9A shows Domain III of one subunit from the post-fusion structure shaded black and grey while the remaining parts of RSV F are in white. Structural elements that do not significantly change betweeen pre- and post-fusion are in black while HRA (labeled with arrow), which refolds in the transition from the pre- to post-fusion conformation, is lighter grey. Motavizumab epitopes on two subunits are also labeled. A third Motavizumab epitope is present on the trimer surface, but is not easily visible in this orientation. The Motavizumab epitope a5 and a6 helices are labeled on one example. Fig. 9B shows Domain III of the pre-fusion model shaded as in A. The fusion peptide region is shaded and labeled FP. The HRA region is broken into structural elements al, a2, a3, βΐ and β2; labeled and shaded grey for one subunit. In both the pre-fusion and post-fusion structures, the a5 and a6 helices of the Motavizumab epitope are surface exposed. However, in the pre-fusion model, the HRC loop may need to shift to accommodate antibody binding (as indicated by the arrow).
[027] FIG. 10 shows a model of neutralizing antibody 101 F bound to the post- fusion RSV F trimer. FIG. 10A shows the peptide (residues 431-435) (SEQ ID NO:37) from the 101F Fab-peptide complex structure (PDB code 3041 21) superposed on equivalent residues of the RSV F structure (β-strand 20 to β-strand 21). FIG. 10B is a ribbon representation of a model of the 101F Fab bound to the RSV F post-fusion trimer. 101F Fab VH and VL domains are labeled; RSV F β-strand 20 and β-strand 21 and labeled as in A. The remaining parts of RSV F are in white. FIG. 10B discloses "IIKTF" as SEQ ID NO: 37.
[028] FIGS. 11 A-C show that residues within appropriate distances to form disulfides can be identified, based on the current model of RSV F pre-fusion, can be identified. FIG. 11A (Center), The pre-fusion RSV F model is shaded/colored to show structural features which are labeled ( HRB, HRA, Dili). FIG. 11B (Left) is a zoom-in view of the packing of HRA on domain III in the pre-fusion model. The paired numbers indicate residues in close proximity which, if mutated to cysteines could form a disulfide bond. FIG. l lC (Right) is a zoom-in view of the packing of the HRB -stalk on domains I and III (white). The paired numbers indicate residues which, if mutated to cysteines could form a disulfide bond. Amino acid residues 165 and 296, and 56 and 164 are not at ideal distances to one another, in the pre-fusion model, to form disulfide bonds, but are in correct orientation and can form disulfides if the model is biased by the PIV5 structure, on which the model was built.
[029] FIG. 12 shows a negative stained electron micrograph of the HRB-deleted RSV F construct (RSV F delHRB HIS, SEQ ID NO:28). Electron microscopy of the HRB- deleted RSV F construct demonstrated the RSV F protein formed rosettes, likely through the fusion peptide. The formation of rosettes through the fusion peptide is a feature of post- fusion RSV F rather than a predicted behavior of pre-fusion F proteins (Ruiz-Arguello et al. 2004 (142) and Connolly et al, 2006 (144)). This result shows the HRB-deleted RSV F construct does not appreciably stabilize the protein in the desired pre-fusion conformation.
[030] FIG. 13 shows the structure of RSV F protein in which certain mutations are introduced to inhibit 6-helix bundle formation. Shown is the RSV F post-fusion structure in which the HRB helix has been removed and replaced with a hypothetical random coil (represented by the lines). The elongated HRA helix of the post-fusion RSV F is labeled. The numbers represent potential sites for introduced glycosylation sites or other mutations which interfere with formation of the 6-helix bundle characteristic of the post-fusion structure. A mutation on the HRA helix which interferes with HRB interaction would destabilize the post- fusion conformation, which in turn would cause the protein to remain in the favored pre- fusion conformation.
[031] FIGs. 14 A and B are western blots of cell lysates (14A, showing total expression) or media (14B, showing secreted protein) under boiled and reducing conditions using an anti-His tag antibody. The westerns show the expression of RSV-F proteins, and that proteins with engineered cysteine residues were expressed and contained intra-chain disulfide bonds. Cleavage of RSV F protein from F0 to F1/F2 and secretion from the cell is evidence of proper protein folding of the RSV F proteins. Migrations for uncleaved F0 and cleaved Fl are indicated. The key for gel lane labeling is shown above the blots. (A) Western blot of cell lysate indicating total protein expression. Each protein construct was well expressed by the cell. (B) Western blot of RSV F secreted into the media. The secreted protein was predominantly cleaved (Fl) and the amount of secretion varied among proteins. The results of this analysis indicate that the T58C & V164C, K168C & V296C and M396C & F483C protein constructs were the best expressed/secreted protein constructs. R049: RSV-F fus del R429S I432T K433T S436F trunc (SEQ ID NO:39); R050: RSV-F HRA Disulfide2 I57C S190C trun (SEQ ID NO:40); R051 : RSV-F HRA Disulfide3 T58C V164C trunc (SEQ ID NO:6); R052: RSV-F HRA Disulfide5 K168C V296C trunc (SEQ ID NO:8); R053: RSV- F fus del N262Y N268I K272M R429S I432T K433T S436F trunc (SEQ ID NO:41); R054 RSV-F HRA Disulfidel V56C V164C trunc (SEQ ID NO:4); R055 RSV-F HRA Disulfide4 N165C V296C trunc (SEQ ID NO: 7); R056 RSV-F HRB Disulfide M396C F483C trunc (SEQ ID NO:9).
[032] FIGs. 15 A - C show SEC analysis of RSV F intra-chain disulfide. Postfusion F rosettes and fusion peptide deleted RSV F trimers were used to develop an HPLC-SEC assay to differentiate between rosettes and trimers. (FIG. 15 A) Fusion peptide- stabilized RSV F rosettes migrated with the void volume by SEC (retention time of 5 minutes on Bio- Sil 250 SEC column). Anti-HIS-tag western blotting confirmed that the protein was in the void volume peak. (FIG. 15 B) Fusion peptide-deletion RSV F trimers migrated with an SEC retention time of approximately 6.5 minutes. Anti-HIS-tag western blot similarly confirmed that the protein was in the included volume trimer peak. Although the void peak is larger than the included volume peak, the anti-HIS western shows approximately equal amounts of RSV F are in the two peaks. (FIG. 15 C) These data show that the RSV F T58C V164C construct had a population of cleaved RSV F that was in the form of monodispersed trimers rather than rosettes, suggesting that population of the protein construct was in the prefusion form.
[033] FIGs. 16 A - C show purification and analysis of RSV F protein constructs that contain engineered cysteins. FIG 16 A shows purification of the RSV F N165C/V296C construct. Columns are labeled for flow-through (FT), wash (W), elution (E) and resin (R) from a chelating purification. Unlike other protein constructs that contained introduced disulfide mutations and were expressed in insect cells, N165C/V296C secreted as a cleaved species, similar to its profile when expressed in mammalian cells. FIG. 16 B shows a gel- shift analysis of the K168C/V296C and M396C/F483C RSV F protein constructs. On the left side of the standards are the two constructs run with boiling and reducing agent present. On the right side of the standards, the two constructs are run after boiling with no reducing agent (b/nr) or no boiling and no reducing agent (nb/nr). The western blot shows the protein is largely uncleaved, but that unexpectedly no inter-chain disulfide bonds were formed.
K168C/V296C without boiling shifted to the trimer band, while non-boiled M396C/F483C ran as a monomer band. FIG. 16 C shows a coomasie-stained gel of the K168C/V296C and M396C/F483C RSV F protein constructs with reducing and boiling. Approximately 50% of the material was cleaved.
[034] FIG. 17(A) shows electron microscopy analysis of NDV F (prefusion) with the expected spherical heads for prefusion F, with a few rosette-like aggregates. FIG. 17(B) shows NDV prefusion F forms rod-like crystals. An isolated rod was analyzed and a dataset with -95% completion to -3.7 angstroms was recorded. FIG, 17 (C) shows NDV prefusion F forms bipiramidal crystals (50x50x50 μιη size).
[035] FIGs. 18 A-E show analysis of several RSV F protein constructs. FIG. 18A shows EM analysis of RSV F Del-HRB showing that 100% formed rosettes. The protein eluted from the SEC column in the void/rosette retention peak. FIG. 18(B) shows analysis/purification of the Del-HRB Del-FP RSV F construct. The protein was found in both the void and trimer retention peaks. FIG. 18C shows gel-analysis, which suggests that there was partially cleaved RSV F Del-HRB Del-FP present in both the void and trimer peaks. FIG. 18D shows EM of NDV F (prefusion), which shows the expected spherical heads for pre-fusion F with a few rosette-like aggregates. FIG. 18E shows that RSV F Del- HRB from the SEC trimer peak contains a heterogeneous mix of rosette-like structures, post- fusion crutches and pre-fusion head-like spherical species.
[036] FIG. 19 shows SDS-PAGE analysis of chimeric RSV F/NDV and RSV F/PIV5 F protein constructs. The supernatant from cells transfected with one of the six constructs (1 : RSV-F NDV HRB del fus trunc; 2: RSV-F NDV HRB trunc; 3: RSV-F NDV HRB2 del fus trunc; 4: RSV-F NDV HRB2 trunc; 5: RSV-F PIV5 HRB del fus trunc; 6: RSV-F PIV5 HRB trunc) was analyzed by SDS-PAGE. The constructs were engineered with or without (del fus) fusion peptide. The proteins either had an NDV HRB, an NDV HRB with an additional glycine residue as a linker (HRB2) or PIV5 HRB as indicated. For each construct, a cleaved Fl protein was observed consistent with a processed F protein. One liter expressions of each protein was performed. DETAILED DESCRIPTION OF THE INVENTION
Definitions
[037] As used herein, "pre-fusion" RSV F proteins are RSV F proteins that share general structural architecture more similar to the PIV5 pre-fusion structure rather than the RSV F post-fusion structure. Pre-fusion RSV F proteins include the following
characteristics: the HRA region is packed against domain III in the RSV F head region and/or the HRB region forms a trimer coil-coil stalk in proximity to domains I and II rather than associating with the HRA region in the context of the 6-helix bundle.
[038] As used herein, "post- fusion conformation" of RSV F protein are RSV F proteins that share more general structural architecture with the RSV F post-fusion structure rather than the PIV5 pre-fusion structure. Post- fusion RSV F proteins include an HRA-HRB 6-helix bundle.
[039] As used herein, HRA region in prefusion RSV F is approximately residues 137-239 of RSV F protein (SEQ ID NOS: 1 and 2) and comprises the fusion peptide, helix Oil , helix ot2, helix ot3, helix ot4, strand β ΐ and strand β2. See, FIG. 9B.
[040] As used herein, the HRA helix in post fusion RSV F is formed by approximately residues 155-226 of RSV F protein (SEQ ID NOS: 1 and 2).
[041] As used herein, the fusion peptide is defined by residues 137-154 of RSV F protein (SEQ ID NOS: 1 and 2).
[042] As used herein, helix Oil in the prefusion RSV F HRA region is formed by approximately residues 145-157 of RSV F protein (SEQ ID NOS: 1 and 2).
[043] As used herein, helix ot2 in the prefusion RSV F HRA region is formed by approximately residues 158-167 of RSV F protein (SEQ ID NOS: 1 and 2).
[044] As used herein, helix ot3 in the prefusion RSV F HRA region is formed by approximately residues 168-176 of RSV F protein (SEQ ID NOS: 1 and 2).
[045] As used herein, helix ot4 in the prefusion RSV F HRA region is formed by approximately residues 194-212 of RSV F protein (SEQ ID NOS: 1 and 2).
[046] As used herein, strand βΐ in the prefusion RSV F HRA region is formed by approximately residues 177-184 of RSV F protein (SEQ ID NOS: 1 and 2).
[047] As used herein, strand β2 in the prefusion RSV F HRA region is formed by approximately residues 185-193 of RSV F protein (SEQ ID NOS: 1 and 2).
[048] As used herein, HRB region in RSV F is approximately residues 461-515 of RSV F protein (SEQ ID NOS: 1 and 2) and includes the HRB helix and the HRB linker [049] As used herein, the HRB helix in RSV F is formed by approximately residues 485-515 of RSV F protein (SEQ ID NOS: 1 and 2).
[050] As used herein, the HRB linker in RSV F is formed by approximately residues 461 - 484 of RSV F protein (SEQ ID NOS: 1 and 2).
[051] As used herein, domain I (DI) is formed by approximately residues 26 - 50 and 309 - 401 of RSV F protein (SEQ ID NOS: 1 and 2).
[052] As used herein, domain II (DII) is formed by approximately residues 400 - 460 of RSV F protein (SEQ ID NOS: 1 and 2).
[053] As used herein, domain III (Dili) is formed by approximately residues 51 -98 and 206 - 308, or residues 51 - 308 of RSV F protein (SEQ ID NOS: 1 and 2).
[054] As used herein, a "purified" protein or polypeptide is a protein or polypeptide which is recombinantly or synthetically produced, or produced by its natural host, and has been isolated from other components of the recombinant or synthetic production system or natural host such that the amount of the protein relative to other macromolecular components present in a composition is substantially higher than that present in a crude preparation. In general, a purified protein will be at least about 50% homogeneous and more preferably at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95% or substantially homogeneous.
[055] As used herein, "substantially free of lipids and lipoproteins" refers to compositions, proteins and polypeptides that are at least about 95% free of lipids and lipoproteins on a mass basis when protein and/or polypeptide (e.g., RSV F polypeptide) purity is observed on an SDS PAGE gel and total protein content is measured using either UV280 absorption or BCA analysis, and lipid and lipoprotein content is determined using the Phospholipase C assay (Wako, code no. 433-36201).
[056] As used herein, "close proximity" refers to a distance of not more than about 10A, not more than about 8 A, not more than about 6A, not more than about 4A, or not more than about 2A. When two or more amino acid residues are in close proximity, the distance between the alpha carbons of the amino acid residues are is more than about 10A, not more than about 8A, not more than about 6A, not more than about 4A, or not more than about 2A.
[057] Features of RSV F protein suitable for use in this invention are described herein with reference to particular amino acids that are identified by the position of the amino acid in the sequence of RSV F protein from the A2 strain (SEQ ID NO: 1). RSV F proteins can have the amino acid sequence of the F protein from the A2 strain or any other desired strain. When the F protein from a strain other than the A2 strain is used, the amino acids of the F protein are to be numbered with reference to the numbering of the F protein from the A2 strain, with the insertion of gaps as needed. This can be achieved by aligning the sequence of any desired RSV F protein with the F protein of the strain A2. Sequence alignments are preferably produced using the algorithm disclosed by Corpet, Nucleic Acids Research, 1998, 16(22): 10881-10890, using default parameters (Blossum 62 symbol comparison table, gap open penalty: 12, gap extension penalty: 2).
[058] As described and exemplified herein, the 3.2 A x-ray crystal structure of a post- fusion form of RSV F protein has been determined. A model of the pre-fusion form of RSV F protein was made by comparing the RSV F post-fusion x-ray crystal structure to the known structures of the pre- and post-fusion parainfluenza virus F proteins. This model of the pre-fusion form of RSV F reveals structural features that differ from those of prior models of pre-fusion RSV F and allows for rational structure-based design of stabilized pre-fusion forms of RSV F.
[059] Accordingly, the invention relates to pre-fusion respiratory syncytial virus F (RSV F) polypeptides and/or proteins, and immunogenic compositions comprising pre-fusion RSV F polypeptides and/or proteins. The invention also relates to methods and use of pre- fusion RSV F polypeptides and/or proteins for inducing an immune response, and or by protective immunity against RSV. The invention also relates to nucleic acids that encode pre-fusion RSV F polypeptides and/or proteins.
[060] Generally, the immunogenic compositions comprise pre-fusion RSV F polypeptides and/or proteins that elicit neutralizing antibodies. For example, antibodies that bind to the same epitopes as Palivizumab, Motavizumab and 101F.
[061] Pre-fusion and post-fusion PIV F structures reveal en bloc shifts of domains and large rearrangements of HRA and HRB. In domain III of the pre-fusion PIV5 structure, HRA folds into three a-helices and two β-strands rather than the long post-fusion HRA helix (Yin et al, 2006). However, when pre-fusion and post-fusion conformations of individual PIV F domains are compared, the non-rearranging parts superimpose well. Superimposing post- fusion RSV F domains on their pre-fusion PIV5 F counterparts did not result in major clashes and positioned all the pairs of cysteines that form interdomain disulfide bonds in proximity to each other. The pre-fusion RSV F model obtained by thus combining information from the post- fusion RSV F x-ray crystal structure and the pre-fusion PIV5 F structure revealed a feature not apparent from prior homology models of pre-fusion RSV F based solely on the PIV5 pre-fusion structure (McLellan et al NSMB 2010 (141)). The helices of the Palivizumab/Motivizumab epitope are exposed on the surface of the pre-fusion RSV F trimer model, as they are on post-fusion RSV F trimer x-ray crystal structure (Figure 9). In our pre-fusion RSV F model, the loop connecting β4 and HRC (part of domain III) could hinder access of Palivizumab or Motavizumab to their epitope. However, it is likely that the loop has sufficient flexibility to adopt an alternative conformation that permits antibody binding (Figure 9B).
[062] The pre-fusion model disclosed herein, which is based on the RSV F post- fusion x-ray crystal structure and the PIV5 prefusion structure (Yin et al, 2006 (145)), shows that the elongated HRA helix of the post-fusion RSV F (residues 137-212) folds into strands and helices similar to the PIV5 pre-fusion crystal structure. The fusion peptide of RSV F, residues 137-154, forms a coil and helix that is packed into the RSV F pre-fusion head. Four helices are formed; helix al is approximately residues 145-157, helix a2 is approximately residues 158-167, helix a3 is approximately residues 168-176 and helix a4 is approximately residues 194-212. Two strands are formed; strand bl is approximately residues 177-184, strand b2 is approximately residues 185-193 (Figure 9).
Pre-fusion Conformation
[055] The invention includes pre-fusion RSV F polypeptides and proteins and immunogenic compositions that contain pre-fusion RSV F polypeptides and proteins. The RSV F protein and polypeptides can contain 1 or more amino acid replacements, deletions and/or additions that stabilize the pre-fusion conformation or destabilize the post-fusion conformation, for example, a pre-fusion RSV F stabilized with disulfide bonds, or a prefusion RSV F formed by destabilizing the post- fusion conformation.
Stabilization through disulfide bonds
[056] The RSV F pre-fusion model may be used as a guide to select amino acid residues that are in close proximity to each other in the pre-fusion conformation and that are no longer in close proximity in the post-fusion conformation. Such amino acids may be mutated to cysteine residues to allow disulfide formation that stabilizes the prefusion conformation, for example by preventing the HRB helix from associating with the HRA helix, thus preventing refolding to the post-fusion conformation.
[057] A stabilized pre-fusion RSV F protein of the invention may comprise a disulfide bond between any two structural elements, or between one structural element and the remainder of the RSV F protein, or between a structural element of one subunit of a trimer and a structural element of another subunit of the same trimer. Generally, a first amino acid in one structural element and a second amino acid that is in a different structural element, or the same structural element on a separate monomer, and that is also in close proximity to the first amino acid in the prefusion model are selected for replacement with cysteine. The distance between the residues (e.g., the alpha carbons) can be less than about 10A, less than about 8A, less than about 6A, less than about 5 A, less than about 4A, or less than about 3A. The cysteine replacements of the first amino acid and the second amino acid, and a disulfide bond between them can be modeled. The length of the modeled disulfide bond, in some embodiments, does not exactly match the ~2A length considered to be optimal for disulfide bonds. Preferably, the modeled disulfide bond length (distance between sulfur nuclei) is about 0.5A-3.5A, about 1.0A-3.0A, or about 1.5A-2.5A, which, due to structural flexibility, are expected to form disulfide bonds in the protein.
[058] In one embodiment, pre-fusion RSV F protein may be stabilized in the prefusion conformation through the introduction of at least one cysteine mutation in a first structural element in close proximity to at least one other cysteine (natural or introduced) in a second structural element or the remaining RSV F head region. Disulfide bonds form between the introduced cysteine that prevent the post- fusion HRA-HRB six-helix bundle from forming. For example, pre-fusion RSV F protein may be stabilized in the pre-fusion conformation through the introduction of at least one cysteine mutation in the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand βΐ, strand β2, DI, DII, or Dili in close proximity to at least one other cysteine (natural or introduced) in a different structural region (e.g., selected from the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand βΐ, strand β2, DI, DII, or Dili), thereby forming one or more disulfide bridges that would prevent the post- fusion HRA-HRB six -helix bundle from forming.
[059] The cysteines may be introduced to the HRB or the HRB linker to create disulfide bonds between the cysteines. In one embodiment, one or more cysteines may be introduced to the HRB linker and helix region (approximately residues 452 to 515) to form disulfides with portions of the RSV F head region. In another embodiment, a disulfide bond between the HRB linker or helix and the remainder of the RSV F protein may be used to stabilize the protein in the pre-fusion conformation. In a preferred embodiment, a disulfide bridge is formed between the HRB pre-fusion stalk and the DI or DII region at the "top" of the head (e.g., M396C + F483C). [060] In a preferred embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, M396C and F483C, thereby comprising a disulfide bond between the HRB pre-fusion stalk and the DI region.
[061] In other preferred embodiments, a disulfide bridge is formed between the HRA region and Dili region. For example, the RSV F protein can contain amino acid
replacements selected from the group consisting of V56C + V164C, I57C + S190C, T58C + V164C, N165C + V296C, K168C + V296C, and combinations thereof.
[062] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the HRA region, and a second cysteine (natural or introduced) in the fusion peptide, helix al, helix a2, helix a3, helix a4, strand βΐ, strand β2 of the pre-fusion HRA region, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post fusion HRA-HRB six-helix bundle from forming.
[063] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the HRB helix region, and a second cysteine (natural or introduced) in DI or DII. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six -helix bundle from forming.
[064] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the fusion peptide, and a second cysteine (natural or introduced) in the HRA region, helix al, helix a2, helix a3, helix a4, strand βΐ, strand β2 or Dili. In this
embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA elongated helix from forming.
[065] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the helix al, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix a2, helix a3, helix a4, strand βΐ, strand β2, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[066] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a2, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al , helix a3, helix a4, strand βΐ, strand β2, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[067] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a3, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al , helix a2, helix a4, strand βΐ, strand β2, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[068] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the helix a4, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al, helix a2, helix a3, strand βΐ, strand β2, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[069] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the strand βΐ, and a second cysteine (natural or introduced) in the HRA region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand β2, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[070] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the strand β2, and a cysteine (natural or introduced) in the HRA helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand βΐ, DI, DII, or Dili. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post-fusion HRA-HRB six-helix bundle from forming.
[071] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the DI region, and a second cysteine (natural or introduced) in the HRB helix region. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
[072] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the DII region, and a second cysteine (natural or introduced) in the HRB helix region. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
[073] In one embodiment, the pre-fusion RSV F protein comprises a first cysteine mutation in the Dili region, and a second cysteine (natural or introduced) in the HRA helix region. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six-helix bundle from forming.
[074] In another embodiment, the pre-fusion RSV F protein comprises a first introduced cysteine in the HRA helix region, HRB helix region, the fusion peptide, helix al, helix a2, helix a3, helix a4, strand βΐ, strand β2, DI, DII, or Dili region and a second cysteine (natural or introduced) in any other region of the RSV F protein that is in close proximity to the introduced cysteine. In this embodiment, the protein comprises a disulfide bond between the first and second cysteine that prevents the post- fusion HRA-HRB six -helix bundle from forming.
[075] In a specific embodiment, the pre-fusion RSV F protein comprises two cysteine mutations selected from the group consisting of V56C + V164C, I57C + S190C, T58C+V164C, N165C+V296C, and K168C + V296C, and combinations thereof, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[076] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, V56C and V164C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[077] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, I57C and S190C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[078] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, T58C and V164C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[079] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, N165C and T296C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[080] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, K168C and T296C, thereby comprising a disulfide bridge between the HRA region and the Dili region.
[081] In one embodiment, the pre-fusion RSV F protein comprises two cysteine mutations, M396C + F483C, thereby comprising a disulfide bridge between the HRB region and the DII region.
[082] The RSV F pre-fusion protein of the present invention is stabilized in the pre- fusion conformation by mutations that stabilize the pre-fusion subunit, which forms trimers.
[083] In some embodiments, the RSV F pre-fusion protein of the present invention is a trimer of RSV F monomers, and pre-fusion conformation is stabilized by one or more disulfide bonds between cysteine residues that are introduced into different monomers.
[084] Exemplary amino acid sequences of RSV F monomers that contain introduced cysteine residues that stabilize the pre-fusion conformation are presented below (SEQ ID NOS: 4-9). The presented sequences contain a signal peptide and a HIS tag
(GGSAGSGHHHHHH; SEQ ID NO:3). The pre-fusion RSV F protein of the invention can contain any of the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
>RSV F HRA disulfidel (V56C + V164C) (SEQ ID NO: 4)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSCITIELSNIKEN KCNGTDA VKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFM YTLNNAKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGECNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH
H
>RSV F HRA disulfide2 (I57C + S190C) (SEQ ID NO: 5)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVCTIELSNIKEN KCNGTDA VKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFM YTLNNAKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSBVLHLEGEV KIKSALLSTNKAWSLSNGVSVLTCBVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH
H
>RSV F HRA disulfide3 (T58C + V164C) (SEQ ID NO: 6)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVICIELSNIKEN KCNGTDA VKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFM YTLNNAKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGECNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH
H
>RSV F HRA disulfide4 (N165C + V296C) (SEQ ID NO: 7)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDA VKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFM YTLNNAKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSBVLHLEGEVCKIKSALLSTNKAWSLSNGVSVLTSBVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEECLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH
H
>RSV F HRA disulfides (K168C + V296C) (SEQ ID NO: 8)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATIWRARRELPRFM YTL AKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSBVLHLEGEV KICSALLSTNKAWSLSNGVSVLTSBVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEECLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH
H
>RSV F HRB disulfide (M396C + F483C) (SEQ ID NO: 9)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDA VKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFM YTLNNAKKT VTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEV KIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSV AGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYWQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM SLTLPSEVNLCNVDIFNPKYDCKICTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYV KQEGKSLYV KGEPIINFYDPLVCPSDEFDASISQV EKINQSLAFIRKSDELLHNV AGKSTTNGGSAGSGHHHHH H
Destabilization of post-fusion RSV F
[055] A major feature of the RSV F post-fusion structure is the 6-helix bundle in the stalk region. In the post-fusion conformation, the three HRA helices and the three HRB helices form a very stable 6-helix bundle. An alternative strategy for producing a stabilized pre-fusion RSV F protein of the invention, is by destabilizing the post-fusion 6-helix bundle, and/or preventing the 6-helix bundle formation (e.g., through deletion of the HRB helix, introduction of point mutations, addition of glycosylation or other modification sites).
[056] The 6-helix bundle formation may be prevented by deleting the HRA helix or the HRB helix.
[057] Preferably, the HRB helical region is deleted or mutated to prevent formation of the post-fusion conformation. The HRB region forms the stalk of the RSV F pre-fusion conformation, is in close proximity to the viral membrane and likely does not contain
important neutralizing epitopes. Deletion of the HRB helix (residues 484 and C-terminal) may prevent the refolding of the RSV F protein from the pre-fusion state to the post- fusion state.
[058] A stabilized pre-fusion RSV F protein of the invention may comprise the RSV ectodomain sequence with the HRB region deleted or mutated, and preferably further
comprises an additional mutation or deletion to the remaining ectodomain sequence. For example, the RSV ectodomain may comprise one or more introduced cysteines to create disulfide bridges that stabilize the prefusion structure as described herein, mutated or deleted furin cleavage sites, mutated or deleted fusion peptide sequence, or other mutations previously described in WO 2011/008974, incorporated herein in its entirety. The RSV ectodomain may be the ectodomain of a naturally occurring RSV F protein, or it may contain mutations in addition to the deletions and/or mutations of the HRA or HRB region.
[059] In one embodiment, the stabilized pre-fusion RSV F protein comprises an ectodomain of a naturally occurring RSV F protein in which the HRB region is deleted and one or more mutations that prevent cleavage at one or both of the furin cleavage sites (i.e, amino acids 109 and 136 of SEQ ID NOS: l and 2) are present.
[060] In one embodiment, the stabilized pre-fusion RSV F protein comprises an ectodomain of a naturally occurring RSV F protein in which the HRB region is deleted and the fusion peptide is mutated (amino acids 137 and 153 of SEQ ID NOS: 1 or 2). For example, this region can be deleted in whole or in part.
[061] In another embodiment, the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region and the fusion peptide is deleted, in whole or in part.
[062] In another embodiment, the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and an oligomerization sequence has been added. When an oligomerization sequence is present, it is preferably a trimerization sequence. Suitable oligomerization sequences are well known in the art and include, for example, the coiled coil of the yeast GCN4 leucine zipper protein, trimerizing sequence from bacteriophage T4 fibritin ("foldon"), and the trimer domain of influenza HA.
[063] In another embodiment, the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and the p27 region is mutated (amino acids 110-136 of SEQ ID NOS: 1 or 2), including deletion of the p27 region in whole or in part. For example, lysine and/or arginine residues in the p27 region (about amino acids 110-136 of SEQ ID NOS: 1 or 2) can be substituted or deleted.
[064] In another embodiment, the stabilized pre-fusion RSV F protein comprises a wild-type RSV ectodomain in which the HRB region is deleted and an amino acid sequence that provides a protease cleavage site is added. Generally, the amino acid sequence that provides a protease cleavage site will be located within about 60 amino acids, about 50 amino acids, about 40 amino acids, about 30 amino acids, about 20 amino acids, about 10 amino acids, or substantially adjacent to the amino terminus of the transmembrane domain (amino acid 525 of SEQ ID NO: l or 2). [065] An exemplary amino acid sequence of an RSV F monomer in which the fusion peptide and HRB are deleted to stabilize the pre-fusion conformation is presented below (SEQ ID NO: 10). The presented sequence contains a signal peptide and a HIS tag
(GGSAGSGHHHHHH; SEQ ID NO:3). The pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
>RSV F delHRB fusion peptide deletion HIS (SEQ ID NO: 10)
MELLILKA AITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELS
NIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAT RARRELPRFM YTL AKK
TNVTLSKKRKRRSAIASGVAVSBVLHLEGEV KIKSALLSTNKAWSLSNGVSVLTSBVLDL
KNYIDKQLLPIV KQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSEL
LSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYWQLPLYGVIDTPCWKLHTS
PLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCBVQSNRVFCDTM SLTLPSEV L
CNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS
NKGVDTVSVGNTLYYV KQEGKSLYVKGEPIINFYDPLVFPSGGSAGSGHHHHHH
[066] The stabilized pre-fusion RSV F protein of the invention may also be formed by hindering 6-helix bundle formation in the HRA or HRB regions (approximately residues 154-212 and 484 to 513, respectively) through engineered point mutations or introduction of glycosylation sites (e.g., AsnXaaSer/Thr; SEQ ID NO:l 1) or other modification sites (e.g., lipidation, phosphorylation). Glycosylation sites, or other post-translational modification sites or point mutations which interfere with 6-helix bundle formation through electrostatic or steric hindrance, can be introduced through the HRA or HRB helical regions. Glycosylation can interfere with 6-helix bundle formation and prevent flipping of the RSV F construct to the post-fusion conformation.
[067] A stabilized pre-fusion RSV F protein of the invention may comprise one or more mutations that form one or more glycosylation sites in the HRA or HRB helical regions. The RSV F protein may contain mutations or deletions in addition to those that introduce the glycosylation sites in the HRA or HRB helical regions.
[068] In one embodiment, the RSV F protein comprises S173N and N175T mutations and the pre-fusion RSV F protein has a glycosylation site on current serine residue 173.
[069] In another embodiment, the RSV F protein comprises a mutation A177T, so that the pre-fusion RSV F protein has a glycosylation site on current residue N175.
[070] In another embodiment, the RSV F protein comprises G184N and S186T mutations and the pre-fusion RSV F protein has a glycosylation site on current residue G184. Chimeric pre-fusion F structures with relevant RSV F epitopes
[071] The invention also relates to chimeric pre-fusion F proteins that contain neutralizing epitopes from RSV F protein. Generally, the chimeric pre-fusion F proteins comprise a stabilized F protein from a different virus, such as the Parainfluenza Virus (PIV1, PIV2, PIV3, PIV4, PIV5), Newcastle Disease Virus (NDV), Sendai virus (SeV), Hendra Virus, Nipah Virus (NiV), human metapneumovirus or avian metapneumovirus, in which portions that are exposed on the surface of the protein are replaced with corresponding portions of RSV F. Preferably, the portions contain neutralizing epitopes of RSV F.
[072] For example, any non-RSV (e.g., parainfluenza virus or metapneumovirus) F protein that is stabilized in the pre-fusion conformation (e.g., by virtue of a GCN trimer domain fused C-terminally to the HRB region), may be used as a template for the protein (i.e., an uncleaved NDV F-GCN fusion protein). For example, the SV5 of PIV5 pre-fusion F protein, described by Yin et al., 2006 (145) or the NDV pre-fusion F described by Swanson et al, 2010 (146) may be used in the chimeric F protein construct. The template may then be mutated to introduce known or suspected neutralizing epitopes of RSV F. Thus, the protein may have a pre-fusion F structure exhibiting the neutralizing epitopes, but not non- neutralizing epitopes, of RSV F. A clear benefit to this construct is that it would not raise non-neutralizing RSV F antibodies.
[073] A pre-fusion chimera protein of the invention may comprise a parainfluenza virus F protein, stabilized in the pre-fusion conformation that is mutated to introduce neutralizing epitopes of RSV F. The parainfluenza virus F protein may be any parainfluenza virus F protein, preferably the SV5 of PIV5 pre-fusion F protein, described by Yin et al., 2006 (147) or the NDV pre-fusion F described by Swanson et al, 2010 (146). Exemplary neutralizing epitopes that may be introduced by mutation include the epitopes disclosed in Table 1. For example, the amino acids that form the epitopes recognized by the antibodies listed in Table 1 can be introduced into the corresponding positions (e.g., identified by structural comparison, such as structure based alignment) of a non RSV-F protein (e.g., parainfluenza virus F protein or metapneumovirus F protein) that is stabilized in the pre- fusion conformation. For example, the chimeric F protein can contain the RSV F site A epitope or site C epitope. In particular example, the chimeric F protein contains one or more RSV F residues selected from the amino acid residues at positions 262 - 276 of RSV F. In another particular example, the chimeric F protein contains one or more RSV F residues selected from the amino acid residues at positions 429 - 447 of RSV F.
 Table 1. Neutralizing epitopes of RSV F:
Site" mAb Residues Method Reference
A 11 N268I Escape0 (149)
A 151 K272N Escape (150)
A 1129 S275F Escape (150)
A 1153 N262S Escape (150)
A 1200 K272N Escape (150)
A 1214 N276Y Escape (150)
A 1237 N276Y Escape (150)
A 47F N262Y, N268I Escape (151)
A 7C2 K272E, K272T Escape (149)
A B4 K272T Escape (149)
A Fab 19d I266M Escape (149)
A AK13A2 N262Y Escape (149)
A PVZe K272M, K272Q, N268I Escape (152)
A PVZe K272M, K272T, S275F Engineeredf (153)
A MVZS N262, N268, D269, K272, S275 Structure11 (141)
C 7.936 I432T, K433T, V447A Escape (154)
C 9.432 S436F Escape (154)
C 19d R429S Escape (149)
C 19d R429K, R429S, G430A Engineered (153)
C 20 R429S Escape (149)
C 101F K433T Escape (155)
C 101F K433D, K433L, K433N, K433Q, K433R Engineered (153)
C 101F R429, 1431, 1432, K433, T434, F435, S436, Structure (148)
N437
a Results of studies using peptide binding or peptide inhibition are not included in this table. b Sites are based on the competition and cross-neutralization analysis of Beeler et al., 1989 (156).
0 An escape mutation is included if it is the sole mutation in an antibody-resistant strain.
d Fabl9 and 19 are unrelated antibodies. The similar names are coincidental.
e Palivizumab
f Engineered mutations in intact recombinant RSV F that allowed intact processing, full fusion activity and reduced monoclonal antibody binding to less than 15% of wild type are included. s Motavizumab
h Residues from peptides in peptide-Fab complex structures are included if either their side chain or backbone atoms make significant contact with the antibody. The biological significance of the peptide-antibody interactions observed in these structural studies has been confirmed by other techniques.
[074] In one embodiment, the chimeric F protein of the invention comprises the HRA region of RSV F (residues 137-212) in place of the equivalent HRA residues of NDV- GCN pre-fusion F. Thus, prefusion F protein (NDV-GCN) is expressed with potential neutralizing epitope sites (HRA region of RSV F) on the top of the pre-fusion F head, permitting neutralizing RSV F antibodies to be elicited. Additional neutralizing epitopes may be added if desired, for example the motavizumab epitope or the 10 IF epitope. [075] An exemplary amino acid sequence of a chimeric protein containing prefusion NDV F mutated to include RSV F HRA amino acid sequences is presented below (SEQ ID
NO: 13). The presented sequences contain a signal peptide, a GCN-trimerization domain and a HIS tag. The chimeric pre-fusion F protein of the invention can contain the amino acid sequence shown below, with or without the signal peptide and/or GCN-trimerization domain and/or HIS tag.
NDV RSV HRA prefusion (underlined portion is RSV HRA, italicized portion is C-terminal GCN trimeric domain and HIS6 (SEQ ID NO: 12) affinity purification tag) (SEQ ID NO: 13).
MGSRSSTRIPVPLMLTVRVMLALSCVCPTSALDGRPLAAAGIVVTGDKAVNIYTSSQTGSIII
KLLPNMPKDKEACAKAPLEAYNRTLTTLLTPLGDSIRRIOESVTTSGGGKOGRLIGAIIGFLG
FLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK
QLLPIVNKQSCIKITQQVGVELNLYLTELTTVFGPQITSPALTQLTIQALYNLAGGNMDYLLT
KLGVGNNQLSSLISSGLITGNPILYDSQTQLLGIQVTLPSVGNLNNMRATYLETLSVSTTKGF
ASALVPKVVTQVGSVIEELDTSYCIETDLDLYCTRIVTFPMSPGIYSCLSGNTSACMYSKTEG
ALTTPYMTLKGSVIANCKMTTCRCADPPGIISQNYGEAVSLIDRQSCNILSLDGITLRLSGEFD
ATYQKNISIQDSQVIVTGNLDISTELGNVNNSISNALDKLEESNSKLDKVED^ffiE/L^/rHffiN
EIARIKKLIGEA GGPLVPRGSHHHHHH
The RSV F glycoprotein
[076] The F glycoprotein of RSV directs viral penetration by fusion between the virion envelope and the host cell plasma membrane. It is a type I single-pass integral
membrane protein having four general domains: N-terminal ER-translocating signal sequence (SS), ectodomain (ED), transmembrane domain (TM), and a cytoplasmic tail (CT). CT
contains a single palmitoylated cysteine residue. The sequence of F protein is highly
conserved among RSV isolates, but is constantly evolving (7). Unlike most
paramyxoviruses, the F protein in RSV can mediate entry and syncytium formation
independent of the other viral proteins (ΗΝ is usually necessary in addition to F in other paramyxoviruses).
[077] The hRSV F mRNA is translated into a 574 amino acid precursor protein
designated F0, which contains a signal peptide sequence at the N-terminus that is removed by a signal peptidase in the endoplasmic reticulum. Fo is cleaved at two sites (a.a. 109/110 and 136/137) by cellular proteases (in particular furin) in the trans-Golgi, removing a short
glycosylated intervening sequence and generating two subunits designated Fi (-50 kDa; C- terminus; residues 137-574) and F2 (-20 kDa; N- terminus; residues 1-109) (See, e.g. , FIG.
4A). Fi contains a hydrophobic fusion peptide at its N-terminus and also two hydrophobic heptad-repeat regions (HRA and HRB). HRA is near the fusion peptide and HRB is near to the transmembrane domain (See, e.g. , FIG. 4A). The Fi-F2 heterodimers are assembled as homotrimers in the virion.
[078] RSV exists as a single serotype but has two antigenic subgroups: A and B. The F glycoproteins of the two groups are about 90% identical. The A subgroup, the B subgroup, or a combination or hybrid of both can be used in the invention. An example sequence for the A subgroup is SEQ ID NO: 1 (A2 strain; GenBank GI: 138251 ; Swiss Prot P03420), and for the B subgroup is SEQ ID NO: 2 (18537 strain; GI: 138250; Swiss Prot P13843). SEQ ID NO: l and SEQ ID NO:2 are both 574 amino acid sequences. The signal peptide in A2 strain is a.a. 1-21, but in 18537 strain it is 1-22. In both sequences the TM domain is from about a.a. 530-550, but has alternatively been reported as 525-548.
SEQ ID NO: 1
1 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIE 60
61 LSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPPTNNRARRELPRFMNYTLN 120
121 NAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAWS 180
181 LSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCS ISNIETVIEFQQKNNRLLEITREFSVN 240
241 AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYS IMSI IKEEVLAYV 300
301 VQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKV 360
361 QSNRVFCDTMNSLTLPSEINLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKT 420
421 KCTASNKNRGI IKTFSNGCDYVSNKGMDTVSVGNTLYYVNKQEGKSLYVKGEPI INFYDP 480
481 LVFPSDEFDAS ISQVNEKINQSLAF IRKSDELLHNVNAGKSTTNIMITTI I IVI IVILLS 540
541 LIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN 574
SEQ ID NO: 2
1 MELLIHRSSAIFLTLAVNALYLTSSQNITEEFYQSTCSAVSRGYFSALRTGWYTSVITIE 60
61 LSNIKETKCNGTDTKVKLIKQELDKYKNAVTELQLLMQNTPAANNRARREAPQYMNYTIN 120
121 TTKNLNVSISKKRKRRFLGFLLGVGSAIASGIAVSKVLHLEGEVNKIKNALLSTNKAWS 180
181 LSNGVSVLTSKVLDLKNYINNRLLPIVNQQSCRISNIETVIEFQQMNSRLLEITREFSVN 240
241 AGVTTPLSTYMLTNSELLSLINDMPITNDQKKLMSSNVQIVRQQSYS IMSI IKEEVLAYV 300
301 VQLPIYGVIDTPCWKLHTSPLCTTNIKEGSNICLTRTDRGWYCDNAGSVSFFPQADTCKV 360
361 QSNRVFCDTMNSLTLPSEVSLCNTDIFNSKYDCKIMTSKTDISSSVITSLGAIVSCYGKT 420
421 KCTASNKNRGI IKTFSNGCDYVSNKGVDTVSVGNTLYYVNKLEGKNLYVKGEPI INYYDP 480
481 LVFPSDEFDAS ISQVNEKINQSLAF IRRSDELLHNVNTGKSTTNIMITTI I IVI IWLLS 540
541 LIAIGLLLYCKAKNTPVTLSKDQLSGINNIAFSK 574
[079] The invention may use any desired RSV F amino acid sequence, such as the amino acid sequence of SEQ ID NO: 1 or 2, or a sequence having identity to SEQ ID NO: 1 or 2. Typically it will have at least 75% identity to SEQ ID NO: 1 or 2 e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%,identity to SEQ ID NO: l or 2. The sequence may be found naturally in RSV.
[080] Where the invention uses an ectodomain of F protein, in whole or in part, it may comprise:
(i) a polypeptide comprising about amino acid 22-525 of SEQ ID NO: 1. (ii) a polypeptide comprising about amino acids 23-525 of SEQ ID NO: 2.
(iii) a polypeptide comprising an amino acid sequence having at least 75% identity (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% identity) to (i) or (ii).
(iv) a polypeptide comprising a fragment of (i), (ii) or (iii), wherein the fragment comprises at least one F protein epitope. The fragment will usually be at least about 100 amino acids long, e.g. , at least about 150, at least about 200, at least about 250, at least about 300, at least about 350, at least about 400, at least about 450 amino acids long.
[081] The ectodomain can be an Fo form with or without the signal peptide, or can comprise two separate peptide chains (e.g., an Fi subunit and a F2 subunit) that are associated with each other, for example, the subunits may be linked by a disulfide bridge. Accordingly, all or a portion of about amino acid 101 to about 161, such as amino acids 110-136, may be absent from the ectodomain. Thus the ectodomain, in whole or in part, can comprise:
(v) a first peptide chain and a second peptide chain that is associated with the first polypeptide chain, where the first peptide chain comprises an amino acid sequence having at least 75% identity (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or even 100% identity) to about amino acid 22 to about amino acid 101 of SEQ ID NO: 1 or to about amino acid 23 to about amino acid 101 of SEQ ID NO: 2, and the second peptide chain comprises an amino acid sequence having at least 75% identity (e.g. , at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, or even 100% identity) to about amino acid 162 to about 525 of SEQ ID NO: 1 or to about amino acid 162 to 525 of SEQ ID NO: 2.
(vi) a first peptide chain and a second peptide chain that is associated with the first polypeptide chain, where the first peptide chain comprises an amino acid sequence comprising a fragment of about amino acid 22 to about amino acid 101 of SEQ ID NO: 1 or of about amino acid 23 to about amino acid 109 of SEQ ID NO: 2, and the second peptide chain comprises a fragment of about amino acid 162 to about amino acid 525 of SEQ ID NO: 1 or of about amino acid 161 to about amino acid 525 of SEQ ID NO: 2. One or both of the fragments will comprise at least one F protein epitope. The fragment in the first peptide chain will usually be at least 20 amino acids long, e.g. , at least 30, at least 40, at least 50, at least 60, at least 70, at least 80 amino acids long. The fragment in the second peptide chain will usually be at least 100 amino acids long, e.g. , at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450 amino acids long.
(vii) a molecule obtainable by furin digestion of (i), (ii), (iii) or (iv). [082] Thus an amino acid sequence used with the invention may be found naturally within RSV F protein (e.g., a soluble RSV F protein lacking TM and CT, about amino acids 522-574 of SEQ ID NOS: 1 or 2), and/or it may have one or more (e.g. , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30) single amino acid mutations (insertions, deletions or substitutions) relative to a natural RSV sequence. For instance, it is known to mutate F proteins to eliminate their furin cleavage sequences, thereby preventing intracellular processing. In certain embodiments, the RSV F protein lacks TM and CT (about amino acids 522-574 of SEQ ID NOS: 1 or 2) and contains one or more (e.g. , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30) single amino acid mutations (insertions, deletions or substitutions) relative to a natural RSV sequence.
Furin-cleavage, Trypsin-cleavage and Fusion Peptide Mutations
[083] If desired, post-fusion RSV F polypeptides or proteins may contain one or more mutations, for example, mutations that prevent cleavage at one or both of the furin cleavage sites (i.e., amino acids 109 and 136 of SEQ ID NOS: 1 and 2), that prevent cleavage of or introduce trypsin cleavage sites, mutations in the p27 region, and/or mutation in the fusion peptide. Such mutations can prevent aggregation of the soluble polypeptides or proteins and thereby facilitate purifications, can prevent cell-cell fusion if the RSV F protein is expressed on the surface of a cell, such as by expression from a viral replicon (e.g., alphavirus replicon particles), or if the RSV F protein is a component of a virus-like particle.
[084] Examples of suitable furin cleavage mutations include replacement of amino acid residues 106 - 109 of SEQ ID NO: 1 or 2 with RARK (SEQ ID NO: 14), RARQ (SEQ ID NO: 15), QAQN (SEQ ID NO: 16), or IEGR (SEQ ID NO: 17). Alternatively, or in addition, amino acid residues 133 - 136 of SEQ ID NO: 1 or 2 can be replaced with RKKK (SEQ ID NO: 18), AAAR, QNQN (SEQ ID NO: 19), QQQR (SEQ ID NO:20) or IEGR (SEQ ID NO: 17). (Δ indicates that the amino acid residue has been deleted.) These furin cleavage mutations can be combined, if desired, with other mutations described herein, such as trypsin cleavage mutations and fusion peptide mutations.
[085] Examples of suitable trypsin cleavage mutations include deletion of any lysine or arginine residue between about position 101 and position 161 of SEQ ID NO: l or 2, or replacement of any such lysine or arginine residue with an amino acid other than lysine or arginine. For example, lysine and/or arginine residues in the p27 region (about amino acids 110-136 of SEQ ID NOS: 1 or 2) can be substituted or deleted, including deletion of the p27 region in whole or in part.
[086] The mutations described herein can be combined, if desired, in any combination. For example, furin mutations can be combined with partial or complete deletion of the fusion peptide region and/or deletion of the HRA or HRB helical region.
[087] In addition to the mutations described above, e.g., furin-cleavage and fusion peptide mutations, or alternatively, soluble RSV F polypeptides or proteins, such as those that lack the transmembrane region and cytoplasmic tail, or HRA and HRB deletions, or cysteine mutations, may contain one or more oligomerization sequences. When an oligomerization sequence is present, it is preferably a trimerization sequence. Suitable oligomerization sequences are well known in the art and include, for example, the coiled coil of the yeast GCN4 leucine zipper protein, trimerizing sequence from bacteriophage T4 fibritin ("foldon"), and the trimer domain of influenza HA. These and other suitable oligomerization sequences are described in greater detail herein.
[088] In particular embodiments, the sequence of the carboxy terminus of the RSV F polypeptide or protein, starting from position 480, is
(GCN) PLVFPSDEFDAS ISQVNEKINQSLAF IRKSDELLHNVNDKIEEILSKIYHIENE IARIKKLIGE (SEQ ID NO: 21 )
(HA) PLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNEKFHQIEKEFSEVEGRIQDLEK (SEQ ID NO : 22 )
(Idealized helix) PLVFPSDEFDASISQINEKINQILAFIRKIDELLHNIN (SEQ ID NO:23) (foldon short)
PLVFPSDEFDAS ISQVNEKINQSLAF IRKSDELLHNVNGSGYIPEAPRDGQAYVRKDGEWVLLSTFL (SEQ ID NO : 24 ) ; or
(foldon long)
PLVFPSDEFDAS ISQVNEKINQSLAF IRKSDELLHNVNNKNDDKGSGYIPEAPRDGQAYVRKDGEWVLLSTFL
(SEQ ID NO:25)
[089] If desired, RSV F polypeptides or proteins that contain a transmembrane region may contain an added amino acid sequence that provides a protease cleavage site. This type of RSV F polypeptide or protein can be produced by expression on the surface of a cell, and recovered in soluble form after cleavage from the cell surface using an appropriate protease. Generally, the amino acid sequence that provides a protease cleavage site will be located within about 60 amino acids, about 50 amino acids, about 40 amino acids, about 30 amino acids, about 20 amino acids, about 10 amino acids, or substantially adjacent to the amino terminus of the transmembrane domain (amino acid 525 of SEQ ID NO: l or 2). Many suitable amino acid sequences that are cleaved by commercially available proteases are well- known in the art. For example, thrombin cleaves the sequence LVPR (SEQ ID NO:26), factor Xa cleaves the sequence IEGR (SEQ ID NO: 17) and enterokinase cleaves the sequence DDDDK (SEQ ID NO:27). These amino acid sequences can be introduced into an RSV F polypeptide.
[090] Immunogenic polypeptides used according to the invention will usually be isolated or purified. Thus, they will not be associated with molecules with which they are normally, if applicable, found in nature. For example, an F protein used with the invention will not be in the form of a RSV virion (although it may be in the form of an artificial virion, such as a virosome or VLP).
[091] Polypeptides will usually be prepared by expression in a recombinant host system. Generally, they (e.g., RSV ecto-domains) are produced by expression of recombinant constructs that encode the ecto-domains in suitable recombinant host cells, although any suitable methods can be used. Suitable recombinant host cells include, for example, insect cells (e.g., Aedes aegypti, Autographa californica, Bombyx mori, Drosophila melanogaster, Spodoptera frugiperda, and Trichoplusia ni), mammalian cells (e.g., human, non-human primate, horse, cow, sheep, dog, cat, and rodent (e.g., hamster), avian cells (e.g., chicken, duck, and geese), bacteria (e.g., E. coli, Bacillus subtilis, and Streptococcus spp.), yeast cells (e.g., Saccharomyces cerevisiae, Candida albicans, Candida maltosa, Hansenual polymorpha, Kluyveromyces fragilis, Kluyveromyces lactis, Pichia guillerimondii, Pichia pastoris, Schizosaccharomyces pombe and Yarrowia lipolytica), Tetrahymena cells (e.g., Tetrahymena thermophila) or combinations thereof. Many suitable insect cells and mammalian cells are well-known in the art. Suitable insect cells include, for example, Sf9 cells, Sf21 cells, Tn5 cells, Schneider S2 cells, and High Five cells (a clonal isolate derived from the parental Trichoplusia ni BTI-TN-5B1-4 cell line (Invitrogen)). Suitable mammalian cells include, for example, Chinese hamster ovary (CHO) cells, human embryonic kidney cells (HEK293 cells, typically transformed by sheared adenovirus type 5 DNA), NIH-3T3 cells, 293-T cells, Vero cells, HeLa cells, PERC.6 cells (ECACC deposit number 96022940), Hep G2 cells, MRC-5 (ATCC CCL-171), WI-38 (ATCC CCL-75), fetal rhesus lung cells (ATCC CL-160), Madin-Darby bovine kidney ("MDBK") cells, Madin-Darby canine kidney ("MDCK") cells (e.g., MDCK (NBL2), ATCC CCL34; or MDCK 33016, DSM ACC 2219), baby hamster kidney (BHK) cells, such as BHK21-F, HKCC cells, and the like. Suitable avian cells include, for example, chicken embryonic stem cells (e.g., EBx® cells), chicken embryonic fibroblasts, chicken embryonic germ cells, duck cells (e.g., AGE1.CR and AGEl .CR.pIX cell lines (ProBioGen) which are described, for example, in Vaccine 27:4975- 4982 (2009) and WO2005/042728), EB66 cells, and the like.
[092] Suitable insect cell expression systems, such as baculovirus systems, are known to those of skill in the art and described in, e.g. , Summers and Smith, Texas
Agricultural Experiment Station Bulletin No. 1555 (1987). Materials and methods for baculovirus/insert cell expression systems are commercially available in kit form from, inter alia, Invitrogen, San Diego CA. Avian cell expression systems are also known to those of skill in the art and described in, e.g. , U.S. Patent Nos. 5,340,740; 5,656,479; 5,830,510; 6,114,168; and 6,500,668; European Patent No. EP 0787180B; European Patent Application No. EP03291813.8 ;WO 03/043415; and WO 03/076601. Similarly, bacterial and mammalian cell expression systems are also known in the art and described in, e.g. , Yeast Genetic Engineering (Barr et al , eds., 1989) Butterworths, London.
[093] Recombinant constructs encoding pre-fusion RSV F protein can be prepared in suitable vectors using conventional methods. A number of suitable vectors for expression of recombinant proteins in insect or mammalian cells are well-known and conventional in the art. Suitable vectors can contain a number of components, including, but not limited to one or more of the following: an origin of replication; a selectable marker gene; one or more expression control elements, such as a transcriptional control element (e.g., a promoter, an enhancer, a terminator), and/or one or more translation signals; and a signal sequence or leader sequence for targeting to the secretory pathway in a selected host cell (e.g., of mammalian origin or from a heterologous mammalian or non-mammalian species). For example, for expression in insect cells a suitable baculovirus expression vector, such as pFastBac (Invitrogen), is used to produce recombinant baculovirus particles. The baculovirus particles are amplified and used to infect insect cells to express recombinant protein. For expression in mammalian cells, a vector that will drive expression of the construct in the desired mammalian host cell (e.g., Chinese hamster ovary cells) is used.
[094] Pre-fusion RSV F protein polypeptides can be purified using any suitable methods. For example, methods for purifying pre-fusion RSV F polypeptides by
immunoaffinity chromatography are known in the art. Ruiz-Arguello et al, J. Gen. Virol, §5:3677-3687 (2004). Suitable methods for purifying desired proteins including precipitation and various types of chromatography, such as hydrophobic interaction, ion exchange, affinity, chelating and size exclusion are well-known in the art. Suitable purification schemes can be created using two or more of these or other suitable methods. If desired, the precision RSV F protein polypeptides can include a "tag" that facilitates purification, such as an epitope tag or a HIS tag. Such tagged polypeptides can conveniently be purified, for example from conditioned media, by chelating chromatography or affinity chromatography.
[095] The pre-fusion RSV F polypeptides may also be produced in situ by expression of nucleic acids that encode them in the cells of a subject. For example, by expression of a self-replicating RNA described herein.
[096] Polypeptides may include additional sequences in addition to the pre-fusion RSV sequences. For example, a polypeptide may include a sequence to facilitate purification {e.g., a poly-His sequence). Similarly, for expression purposes, the natural leader peptide of F protein may be substituted for a different one. For example, reference 6 used a honeybee melittin leader peptide in place of the natural one.
Self-Replicating RNA
[097] The pre-fusion RSV-F polypeptides described herein can be produced by expression of recombinant nucleic acids that encode the polypeptides in the cells of a subject. Preferred nucleic acids that can be administered to a subject to cause the production of pre- fusion RSV-F polypeptides are self-replicating RNA molecules. The self -replicating RNA molecules of the invention are based on the genomic RNA of RNA viruses, but lack the genes encoding one or more structural proteins. The self -replicating RNA molecules are capable of being translated to produce non-structural proteins of the RNA virus and heterologous proteins encoded by the self -replicating RNA.
[098] The self -replicating RNA generally contains at least one or more genes selected from the group consisting of viral replicase, viral proteases, viral helicases and other nonstructural viral proteins, and also comprise 5'- and 3 '-end cis-active replication sequences, and if desired, a heterologous sequences that encode a desired amino acid sequences (e.g., a protein, an antigen). A subgenomic promoter that directs expression of the heterologous sequence can be included in the self -replicating RNA. If desired, the heterologous sequence may be fused in frame to other coding regions in the self-replicating RNA and/or may be under the control of an internal ribosome entry site (IRES).
[099] Self -replicating RNA molecules of the invention can be designed so that the self -replicating RNA molecule cannot induce production of infectious viral particles. This can be achieved, for example, by omitting one or more viral genes encoding structural proteins that are necessary for the production of viral particles in the self-replicating RNA. For example, when the self-replicating RNA molecule is based on an alpha virus, such as Sinebis virus (SIN), Semliki forest virus and Venezuelan equine encephalitis virus (VEE), one or more genes encoding viral structural proteins, such as capsid and/or envelope glycoproteins, can be omitted. If desired, self -replicating RNA molecules of the invention can be designed to induce production of infectious viral particles that are attenuated or virulent, or to produce viral particles that are capable of a single round of subsequent infection.
[0100] A self -replicating RNA molecule can, when delivered to a vertebrate cell even without any proteins, lead to the production of multiple daughter RNAs by transcription from itself (or from an antisense copy of itself). The self-replicating RNA can be directly translated after delivery to a cell, and this translation provides a RNA-dependent RNA polymerase which then produces transcripts from the delivered RNA. Thus the delivered RNA leads to the production of multiple daughter RNAs. These transcripts are antisense relative to the delivered RNA and may be translated themselves to provide in situ expression of a gene product, or may be transcribed to provide further transcripts with the same sense as the delivered RNA which are translated to provide in situ expression of the encoded RSV-F polypeptide.
[0101] One suitable system for achieving self-replication is to use an alphavirus- based RNA replicon. These + stranded replicons are translated after delivery to a cell to give of a replicase (or replicase-transcriptase). The replicase is translated as a polyprotein which auto cleaves to provide a replication complex which creates genomic - strand copies of the + strand delivered RNA. These - strand transcripts can themselves be transcribed to give further copies of the + stranded parent RNA and also to give a subgenomic transcript which encodes the RSV-F polypeptide. Translation of the subgenomic transcript thus leads to in situ expression of the RSV-F polypeptide by the infected cell. Suitable alphavirus replicons can use a replicase from a sindbis virus, a semliki forest virus, an eastern equine encephalitis virus, a Venezuelan equine encephalitis virus, etc.
[0102] A preferred self -replicating RNA molecule thus encodes (i) a RNA-dependent RNA polymerase which can transcribe RNA from the self-replicating RNA molecule and (ii) an RSV-F polypeptide. The polymerase can be an alphavirus replicase e.g. comprising alphavirus protein nsP4.
[0103] Whereas natural alphavirus genomes encode structural virion proteins in addition to the non structural replicase polyprotein, it is preferred that an alphavirus based self -replicating RNA molecule of the invention does not encode alphavirus structural proteins. Thus the self replicating RNA can lead to the production of genomic RNA copies of itself in a cell, but not to the production of RNA-containing alphavirus virions. The inability to produce these virions means that, unlike a wild-type alphavirus, the self- replicating RNA molecule cannot perpetuate itself in infectious form. The alphavirus structural proteins which are necessary for perpetuation in wild-type viruses are absent from self replicating RNAs of the invention and their place is taken by gene(s) encoding the desired gene product, such that the subgenomic transcript encodes the desired gene product rather than the structural alphavirus virion proteins.
[0104] Thus a self -replicating RNA molecule useful with the invention may have two open reading frames. The first (5') open reading frame encodes a replicase; the second (3') open reading frame encodes an RSV-F polypeptide. In some embodiments the RNA may have additional (downstream) open reading frames e.g. that encode further desired gene products. A self -replicating RNA molecule can have a 5' sequence which is compatible with the encoded replicase.
[0105] In one aspect, the self -replicating RNA molecule is derived from or based on an alphavirus. In other aspects, the self -replicating RNA molecule is derived from or based on a virus other than an alphavirus, preferably, a positive-stranded RNA viruses, and more preferably a picornavirus, flavivirus, rubivirus, pestivirus, hepacivirus, calicivirus, or coronavirus. Suitable wild- type alphavirus sequences are well-known and are available from sequence depositories, such as the American Type Culture Collection, Rockville, Md.
Representative examples of suitable alphaviruses include Aura (ATCC VR-368), Bebaru virus (ATCC VR-600, ATCC VR-1240), Cabassou (ATCC VR-922), Chikungunya virus (ATCC VR-64, ATCC VR-1241), Eastern equine encephalomyelitis virus (ATCC VR-65, ATCC VR-1242), Fort Morgan (ATCC VR-924), Getah virus (ATCC VR-369, ATCC VR- 1243), Kyzylagach (ATCC VR-927), Mayaro (ATCC VR-66), Mayaro virus (ATCC VR- 1277), Middleburg (ATCC VR-370), Mucambo virus (ATCC VR-580, ATCC VR-1244), Ndumu (ATCC VR-371), Pixuna virus (ATCC VR-372, ATCC VR-1245), Ross River virus (ATCC VR-373, ATCC VR-1246), Semliki Forest (ATCC VR-67, ATCC VR-1247), Sindbis virus (ATCC VR-68, ATCC VR-1248), Tonate (ATCC VR-925), Triniti (ATCC VR-469), Una (ATCC VR-374), Venezuelan equine encephalomyelitis (ATCC VR-69, ATCC VR-923, ATCC VR-1250 ATCC VR-1249, ATCC VR-532), Western equine encephalomyelitis (ATCC VR-70, ATCC VR-1251, ATCC VR-622, ATCC VR-1252), Whataroa (ATCC VR- 926), and Y-62-33 (ATCC VR-375). [0106] The self -replicating RNA may be associated with a delivery system. The self- replicating RNA may be administered with or without an adjuvant.
RNA DELIVERY SYSTEMS
[0107] The self -replicating RNA of the invention are suitable for delivery in a variety of modalities, such as naked RNA delivery or in combination with lipids, polymers or other compounds that facilitate entry into the cells. Self-replicating RNA molecules of the present invention can be introduced into target cells or subjects using any suitable technique, e.g., by direct injection, microinjection, electroporation, lipofection, biolystics, and the like. The self- replicating RNA molecule may also be introduced into cells by way of receptor-mediated endocytosis. See e.g. , U.S. Pat. No. 6,090,619; Wu and Wu, J. Biol. Chem., 263: 14621 (1988); and Curiel et al., Proc. Natl. Acad. Sci. USA, 88:8850 (1991). For example, U.S. Pat. No. 6,083,741 discloses introducing an exogenous nucleic acid into mammalian cells by associating the nucleic acid to a polycation moiety (e.g. , poly-L-lysine having 3-100 lysine residues), which is itself coupled to an integrin receptor-binding moiety (e.g. , a cyclic peptide having the sequence Arg-Gly-Asp).
[0108] The self -replicating RNA molecule of the present invention can be delivered into cells via amphiphiles. See e.g., U.S. Pat. No. 6,071 ,890. Typically, a nucleic acid molecule may form a complex with the cationic amphiphile. Mammalian cells contacted with the complex can readily take it up.
[0109] The self -replicating RNA can be delivered as naked RNA (e.g. merely as an aqueous solution of RNA) but, to enhance entry into cells and also subsequent intercellular effects, the self-replicating RNA is preferably administered in combination with a delivery system, such as a particulate or emulsion delivery system. A large number of delivery systems are well known to those of skill in the art. Such delivery systems include, for example liposome-based delivery (Debs and Zhu (1993) WO 93/24640; Mannino and Gould- Fogerite (1988) BioTechniques 6(7): 682-691 ; Rose U.S. Pat. No. 5,279,833; Brigham (1991) WO 91/06309; and Feigner et al. (1987) Proc. Natl. Acad. Sci. USA 84: 7413-7414), as well as use of viral vectors (e.g. , adenoviral (see, e.g., Berns et al. (1995) Ann. NY Acad. Sci. 772: 95-104; Ali et al. (1994) Gene Ther. 1 : 367-384; and Haddada et al. (1995) Curr. Top.
Microbiol. Immunol. 199 (Pt 3): 297-306 for review), papillomaviral, retroviral (see, e.g. , Buchscher et al. (1992) J. Virol. 66(5) 2731-2739; Johann et al. (1992) J. Virol. 66 (5): 1635- 1640 (1992); Sommerfelt et al., (1990) Virol. 176:58-59; Wilson et al. (1989) J. Virol.
63:2374-2378; Miller et al., J. Virol. 65:2220-2224 (1991); Wong-Staal et al, PCT/US94/05700, and Rosenburg and Fauci (1993) in Fundamental Immunology, Third Edition Paul (ed) Raven Press, Ltd., New York and the references therein, and Yu et al., Gene Therapy (1994) supra.), and adeno-associated viral vectors (see, West et al. (1987) Virology 160:38-47; Carter et al. (1989) U.S. Pat. No. 4,797,368; Carter et al. WO 93/24641 (1993); Kotin (1994) Human Gene Therapy 5:793-801 ; Muzyczka (1994) J. Clin. Invst. 94: 1351 and Samulski (supra) for an overview of AAV vectors; see also, Lebkowski, U.S. Pat. No. 5,173,414; Tratschin et al. (1985) Mol. Cell. Biol. 5(11):3251-3260; Tratschin, et al. (1984) Mol. Cell. Biol., 4:2072-2081 ; Hermonat and Muzyczka (1984) Proc. Natl. Acad. Sci. USA, 81 :6466-6470; McLaughlin et al. (1988) and Samulski et al. (1989) J. Virol.,
63:03822-3828), and the like.
[0110] Three particularly useful delivery systems are (i) liposomes (ii) non-toxic and biodegradable polymer microparticles (iii) cationic submicron oil-in-water emulsions.
Liposomes
[0111] Various amphiphilic lipids can form bilayers in an aqueous environment to encapsulate a RNA-containing aqueous core as a liposome. These lipids can have an anionic, cationic or zwitterionic hydrophilic head group. Formation of liposomes from anionic phospholipids dates back to the 1960s, and cationic liposome-forming lipids have been studied since the 1990s. Some phospholipids are anionic whereas other are zwitterionic. Suitable classes of phospholipid include, but are not limited to, phosphatidylethanolamines, phosphatidylcholines, phosphatidylserines, and phosphatidylglycerols, and some useful phospholipids are listed in Table 2. Useful cationic lipids include, but are not limited to, dioleoyl trimethylammonium propane (DOTAP), l ,2-distearyloxy-N,N-dimethyl-3- aminopropane (DSDMA), l ,2-dioleyloxy-N,Ndimethyl-3-aminopropane (DODMA), 1,2- dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1 ,2-dilinolenyloxy-N,N- dimethyl-3-aminopropane (DLenDMA). Zwitterionic lipids include, but are not limited to, acyl zwitterionic lipids and ether zwitterionic lipids. Examples of useful zwitterionic lipids are DPPC, DOPC and dodecylphosphocholine. The lipids can be saturated or unsaturated.
[0112] Liposomes can be formed from a single lipid or from a mixture of lipids. A mixture may comprise (i) a mixture of anionic lipids (ii) a mixture of cationic lipids (iii) a mixture of zwitterionic lipids (iv) a mixture of anionic lipids and cationic lipids (v) a mixture of anionic lipids and zwitterionic lipids (vi) a mixture of zwitterionic lipids and cationic lipids or (vii) a mixture of anionic lipids, cationic lipids and zwitterionic lipids. Similarly, a mixture may comprise both saturated and unsaturated lipids. For example, a mixture may comprise DSPC (zwitterionic, saturated), DlinDMA (cationic, unsaturated), and/or DMPG (anionic, saturated). Where a mixture of lipids is used, not all of the component lipids in the mixture need to be amphiphilic e.g. one or more amphiphilic lipids can be mixed with cholesterol.
[0113] The hydrophilic portion of a lipid can be PEGylated (i.e. modified by covalent attachment of a polyethylene glycol). This modification can increase stability and prevent non-specific adsorption of the liposomes. For instance, lipids can be conjugated to PEG using techniques such as those disclosed in Heyes et al. (2005) J Controlled Release 107:276-287.
[0114] A mixture of DSPC, DlinDMA, PEG-DMPG and cholesterol is used in the examples. A separate aspect of the invention is a liposome comprising DSPC, DlinDMA, PEG-DMG and cholesterol. This liposome preferably encapsulates RNA, such as a self- replicating RNA e.g. encoding an immunogen.
[0115] Liposomes are usually divided into three groups: multilamellar vesicles (MLV); small unilamellar vesicles (SUV); and large unilamellar vesicles (LUV). MLVs have multiple bilayers in each vesicle, forming several separate aqueous compartments. SUVs and LUVs have a single bilayer encapsulating an aqueous core; SUVs typically have a diameter <50nm, and LUVs have a diameter >50nm. Liposomes useful with of the invention are ideally LUVs with a diameter in the range of 50-220nm. For a composition comprising a population of LUVs with different diameters: (i) at least 80% by number should have diameters in the range of 20-220nm, (ii) the average diameter (Zav, by intensity) of the population is ideally in the range of 40-200nm, and/or (iii) the diameters should have a polydispersity index <0.2.
[0116] Techniques for preparing suitable liposomes are well known in the art e.g. see Liposomes: Methods and Protocols, Volume 1 : Pharmaceutical Nanocarriers: Methods and Protocols, (ed. Weissig). Humana Press, 2009. ISBN 160327359X; Liposome Technology, volumes I, II & III. (ed. Gregoriadis). Informa Healthcare, 2006; and Functional Polymer Colloids and Microparticles volume 4 (Microspheres, microcapsules & liposomes), (eds. Arshady & Guyot). Citus Books, 2002. One useful method involves mixing (i) an ethanolic solution of the lipids (ii) an aqueous solution of the nucleic acid and (iii) buffer, followed by mixing, equilibration, dilution and purification (Heyes et al. (2005) J Controlled Release 107:276-87.).
[0117] RNA is preferably encapsulated within the liposomes, and so the liposome forms a outer layer around an aqueous RNA-containing core. This encapsulation has been found to protect RNA from RNase digestion.. The liposomes can include some external RNA (e.g. on the surface of the liposomes), but at least half of the RNA (and ideally all of it) is encapsulated.
Polymeric microparticles
[0118] Various polymers can form microparticles to encapsulate or adsorb RNA. The use of a substantially non-toxic polymer means that a recipient can safely receive the particles, and the use of a biodegradable polymer means that the particles can be metabolised after delivery to avoid long-term persistence. Useful polymers are also sterilisable, to assist in preparing pharmaceutical grade formulations.
[0119] Suitable non-toxic and biodegradable polymers include, but are not limited to, poly(a-hydroxy acids), polyhydroxy butyric acids, polylactones (including
polycaprolactones), polydioxanones, polyvalerolactone, polyorthoesters, poly anhydrides, polycyanoacrylates, tyrosine-derived polycarbonates, polyvinyl-pyrrolidinones or polyester- amides, and combinations thereof.
[0120] In some embodiments, the microparticles are formed from poly(a-hydroxy acids), such as a poly(lactides) ("PLA"), copolymers of lactide and glycolide such as a poly(D,L-lactide-co-glycolide) ("PLG"), and copolymers of D,L-lactide and caprolactone. Useful PLG polymers include those having a lactide/glycolide molar ratio ranging, for example, from 20:80 to 80:20 e.g. 25:75, 40:60, 45:55, 55:45, 60:40, 75:25. Useful PLG polymers include those having a molecular weight between, for example, 5,000-200,000 Da e.g. between 10,000-100,000, 20,000-70,000, 40,000-50,000 Da.
[0121] The microparticles ideally have a diameter in the range of 0.02 μιη to 8μιη. For a composition comprising a population of microparticles with different diameters at least 80% by number should have diameters in the range of 0.03-7μιη.
[0122] Techniques for preparing suitable microparticles are well known in the art e.g. see Functional Polymer Colloids and Microparticles volume 4 (Microspheres, microcapsules & liposomes), (eds. Arshady & Guyot). Citus Books, 2002; Polymers in Drug Delivery, (eds. Uchegbu & Schatzlein). CRC Press, 2006. (in particular chapter 7) and Microparticulate Systems for the Delivery of Proteins and Vaccines, (eds. Cohen & Bernstein). CRC Press, 1996. To facilitate adsorption of RNA, a microparticle may include a cationic surfactant and/or lipid e.g. as disclosed in O'Hagan et al. (2001) J Virologyl5: 9037-9043; and Singh et al. (2003) Pharmaceutical Research 20: 247-251. An alternative way of making polymeric microparticles is by molding and curing e.g. as disclosed in WO2009/132206. [0123] Microparticles of the invention can have a zeta potential of between 40-100 mV.
[0124] RNA can be adsorbed to the microparticles, and adsorption is facilitated by including cationic materials (e.g. cationic lipids) in the microparticle.
Oil-in-water cationic emulsions
[0125] Oil-in-water emulsions are known for adjuvanting influenza vaccines e.g. the MF59™ adjuvant in the FLU AD™ product, and the AS03 adjuvant in the PREPANDRIX™ product. RNA delivery according to the present invention can utilise an oil-in-water emulsion, provided that the emulsion includes one or more cationic molecules. For instance, a cationic lipid can be included in the emulsion to provide a positive droplet surface to which negatively-charged RNA can attach.
[0126] The emulsion comprises one or more oils. Suitable oil(s) include those from, for example, an animal (such as fish) or a vegetable source. The oil is ideally biodegradable (metabolisable) and biocompatible. Sources for vegetable oils include nuts, seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil, the most commonly available, exemplify the nut oils. Jojoba oil can be used e.g. obtained from the jojoba bean. Seed oils include safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like. In the grain group, corn oil is the most readily available, but the oil of other cereal grains such as wheat, oats, rye, rice, teff, triticale and the like may also be used. 6-10 carbon fatty acid esters of glycerol and 1 ,2-propanediol, while not occurring naturally in seed oils, may be prepared by hydrolysis, separation and esterification of the appropriate materials starting from the nut and seed oils. Fats and oils from mammalian milk are metabolizable and so may be used. The procedures for separation, purification, saponification and other means necessary for obtaining pure oils from animal sources are well known in the art.
[0127] Most fish contain metabolizable oils which may be readily recovered. For example, cod liver oil, shark liver oils, and whale oil such as spermaceti exemplify several of the fish oils which may be used herein. A number of branched chain oils are synthesized biochemically in 5-carbon isoprene units and are generally referred to as terpenoids.
Squalane, the saturated analog to squalene, can also be used. Fish oils, including squalene and squalane, are readily available from commercial sources or may be obtained by methods known in the art.
[0128] Other useful oils are the tocopherols, particularly in combination with squalene. Where the oil phase of an emulsion includes a tocopherol, any of the α, β, γ, δ, ε or ξ tocopherols can be used, but a-tocopherols are preferred. D-a-tocopherol and
DL-a-tocopherol can both be used. A preferred a-tocopherol is DL-a-tocopherol. An oil combination comprising squalene and a tocopherol (e.g. DL-a-tocopherol) can be used.
[0129] Preferred emulsions comprise squalene, a shark liver oil which is a branched, unsaturated terpenoid (C30H50; [(C^C^CHCHzCHzCCCIL^CHCHz-k 2,6, 10,15,19,23- hexamethyl-2,6,10,14,18,22-tetracosahexaene; CAS RN 7683-64-9).
[0130] The oil in the emulsion may comprise a combination of oils e.g. squalene and at least one further oil.
[0131] The aqueous component of the emulsion can be plain water (e.g. w.f.i.) or can include further components e.g. solutes. For instance, it may include salts to form a buffer e.g. citrate or phosphate salts, such as sodium salts. Typical buffers include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer; or a citrate buffer. A buffered aqueous phase is preferred, and buffers will typically be included in the 5-20mM range.
[0132] The emulsion also includes a cationic lipid. Preferably this lipid is a surfactant so that it can facilitate formation and stabilisation of the emulsion. Useful cationic lipids generally contains a nitrogen atom that is positively charged under physiological conditions e.g. as a tertiary or quaternary amine. This nitrogen can be in the hydrophilic head group of an amphiphilic surfactant. Useful cationic lipids include, but are not limited to: 1,2- dioleoyloxy-3 -(trimethylammonio)propane (DOTAP) , 3 '- [Ν-(Ν' ,N'-Dimethylaminoethane)- carbamoyl] Cholesterol (DC Cholesterol), dimethyldioctadecyl-ammonium (DDA e.g. the bromide), l,2-Dimyristoyl-3-Trimethyl-AmmoniumPropane (DMTAP),
dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP), distearoyltrimethylammonium propane (DSTAP). Other useful cationic lipids are: benzalkonium chloride (BAK), benzethonium chloride, cetramide (which contains tetradecyltrimethylammonium bromide and possibly small amounts of dedecyltrimethylammonium bromide and hexadecyltrimethyl ammonium bromide), cetylpyridinium chloride (CPC), cetyl trimethylammonium chloride (CTAC), Ν,Ν',Ν'-polyoxyethylene (10)-N-tallow-l,3 -diaminopropane,
dodecyltrimethylammonium bromide, hexadecyltrimethyl-ammonium bromide, mixed alkyl- trimethyl- ammonium bromide, benzyldimethyldodecylammonium chloride,
benzyldimethylhexadecyl-ammonium chloride, benzyltrimethylammonium methoxide, cetyldimethylethylammonium bromide, dimethyldioctadecyl ammonium bromide (DDAB), methylbenzethonium chloride, decamethonium chloride, methyl mixed trialkyl ammonium chloride, methyl trioctylammonium chloride), N,N-dimethyl-N-[2 (2-methyl-4- (1,1, 3 ,3tetramethylbutyl)- phenoxy] -ethoxy)ethyl] -benzenemetha-naminium chloride
(DEBDA), dialkyldimetylammonium salts, [l-(2,3-dioleyloxy)-propyl]- N,N,N,trimethylammonium chloride, l,2-diacyl-3-(trimethylammonio) propane (acyl group=dimyristoyl, dipalmitoyl, distearoyl, dioleoyl), l,2-diacyl-3
(dimethylammonio)propane (acyl group=dimyristoyl, dipalmitoyl, distearoyl, dioleoyl), 1,2- dioleoyl-3-(4'-trimethyl- ammonio)butanoyl-sn-glycerol, 1,2-dioleoyl 3 -succinyl-sn- glycerol choline ester, cholesteryl (4'-trimethylammonio) butanoate), N-alkyl pyridinium salts (e.g. cetylpyridinium bromide and cetylpyridinium chloride), N-alkylpiperidinium salts, dicationic bolaform electrolytes (C12Me6; C12BU6), dialkylglycetylphosphorylcholine, lysolecithin, L- α dioleoylphosphatidylethanolamine, cholesterol hemisuccinate choline ester,
lipopoly amines, including but not limited to dioctadecylamidoglycylspermine (DOGS), dipalmitoyl phosphatidylethanol-amidospermine (DPPES), lipopoly-L (or D)- lysine (LPLL, LPDL), poly (L (or D)-lysine conjugated to N- glutarylphosphatidylethanolamine, didodecyl glutamate ester with pendant amino group (CAGluPhCnN ), ditetradecyl glutamate ester with pendant amino group (C14GIuCnN+), cationic derivatives of cholesterol, including but not limited to cholesteryl-3 β-oxysuccinamidoethylenetrimethylammonium salt, cholesteryl-3 β- oxysuccinamidoethylene-dimethylamine, cholesteryl-3 β- carboxyamidoethylenetrimethylammonium salt, and cholesteryl-3
β-carboxyamidoethylenedimethylamine. Other useful cationic lipids are described in US 2008/0085870 and US 2008/0057080, which are incorporated herein by reference.
[0133] The cationic lipid is preferably biodegradable (metabolisable) and
biocompatible.
[0134] In addition to the oil and cationic lipid, an emulsion can include a non-ionic surfactant and/or a zwitterionic surfactant. Such surfactants include, but are not limited to: the polyoxyethylene sorbitan esters surfactants (commonly referred to as the Tweens), especially polysorbate 20 and polysorbate 80; copolymers of ethylene oxide (EO), propylene oxide (PO), and/or butylene oxide (BO), sold under the DOWFAX™ tradename, such as linear EO/PO block copolymers; octoxynols, which can vary in the number of repeating ethoxy (oxy-l,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, or
t-octylphenoxypolyethoxyethanol) being of particular interest;
(octylphenoxy)polyethoxyethanol (IGEPAL CA-630/NP-40); phospholipids such as phosphatidylcholine (lecithin); polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such as triethyleneglycol monolauryl ether (Brij 30); polyoxyethylene-9-lauryl ether; and sorbitan esters (commonly known as the Spans), such as sorbitan trioleate (Span 85) and sorbitan monolaurate. Preferred surfactants for including in the emulsion are polysorbate 80 (Tween 80; polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100.
[0135] Mixtures of these surfactants can be included in the emulsion e.g. Tween 80/Span 85 mixtures, or Tween 80/Triton-X100 mixtures. A combination of a
polyoxyethylene sorbitan ester such as polyoxyethylene sorbitan monooleate (Tween 80) and an octoxynol such as t-octylphenoxy-polyethoxyethanol (Triton X-100) is also suitable. Another useful combination comprises laureth 9 plus a polyoxyethylene sorbitan ester and/or an octoxynol. Useful mixtures can comprise a surfactant with a HLB value in the range of 10-20 (e.g. polysorbate 80, with a HLB of 15.0) and a surfactant with a HLB value in the range of 1-10 (e.g. sorbitan trioleate, with a HLB of 1.8).
[0136] Preferred amounts of oil (% by volume) in the final emulsion are between 2- 20% e.g. 5-15%, 6-14%, 7-13%, 8-12%. A squalene content of about 4-6% or about 9-11 % is particularly useful.
[0137] Preferred amounts of surfactants (% by weight) in the final emulsion are between 0.001% and 8%. For example: polyoxyethylene sorbitan esters (such as polysorbate 80) 0.2 to 4%, in particular between 0.4-0.6%, between 0.45-0.55%, about 0.5% or between 1.5-2%, between 1.8-2.2%, between 1.9-2.1%, about 2%, or 0.85-0.95%, or about 1 %;
sorbitan esters (such as sorbitan trioleate) 0.02 to 2%, in particular about 0.5% or about 1%; octyl- or nonylphenoxy polyoxyethanols (such as Triton X-100) 0.001 to 0.1%, in particular 0.005 to 0.02%; polyoxyethylene ethers (such as laureth 9) 0.1 to 8%, preferably 0.1 to 10% and in particular 0.1 to 1% or about 0.5%.
[0138] The absolute amounts of oil and surfactant, and their ratio, can be varied within wide limits while still forming an emulsion. A skilled person can easily vary the relative proportions of the components to obtain a desired emulsion, but a weight ratio of between 4: 1 and 5: 1 for oil and surfactant is typical (excess oil).
[0139] An important parameter for ensuring immunostimulatory activity of an emulsion, particularly in large animals, is the oil droplet size (diameter). The most effective emulsions have a droplet size in the submicron range. Suitably the droplet sizes will be in the range 50-750nm. Most usefully the average droplet size is less than 250nm e.g. less than 200nm, less than 150nm. The average droplet size is usefully in the range of 80-180nm. Ideally, at least 80% (by number) of the emulsion's oil droplets are less than 250 nm in diameter, and preferably at least 90%. Apparatuses for determining the average droplet size in an emulsion, and the size distribution, are commercially available. These typically use the techniques of dynamic light scattering and/or single-particle optical sensing e.g. the
Accusizer™ and Nicomp™ series of instruments available from Particle Sizing Systems (Santa Barbara, USA), or the Zetasizer™ instruments from Malvern Instruments (UK), or the Particle Size Distribution Analyzer instruments from Horiba (Kyoto, Japan).
[0140] Ideally, the distribution of droplet sizes (by number) has only one maximum i.e. there is a single population of droplets distributed around an average (mode), rather than having two maxima. Preferred emulsions have a polydispersity of <0.4 e.g. 0.3, 0.2, or less.
[0141] Suitable emulsions with submicron droplets and a narrow size distribution can be obtained by the use of microfluidisation. This technique reduces average oil droplet size by propelling streams of input components through geometrically fixed channels at high pressure and high velocity. These streams contact channel walls, chamber walls and each other. The results shear, impact and cavitation forces cause a reduction in droplet size.
Repeated steps of microfluidisation can be performed until an emulsion with a desired droplet size average and distribution are achieved.
[0142] As an alternative to microfluidisation, thermal methods can be used to cause phase inversion. These methods can also provide a submicron emulsion with a tight particle size distribution.
[0143] Preferred emulsions can be filter sterilized i.e. their droplets can pass through a 220nm filter. As well as providing a sterilization, this procedure also removes any large droplets in the emulsion.
[0144] In certain embodiments, the cationic lipid in the emulsion is DOTAP. The cationic oil-in- water emulsion may comprise from about 0.5 mg/ml to about 25 mg/ml DOTAP. For example, the cationic oil-in- water emulsion may comprise DOTAP at from about 0.5 mg/ml to about 25 mg/ml, from about 0.6 mg/ml to about 25 mg/ml, from about 0.7 mg/ml to about 25 mg/ml, from about 0.8 mg/ml to about 25 mg/ml, from about 0.9 mg/ml to about 25 mg/ml, from about 1.0 mg/ml to about 25 mg/ml, from about 1.1 mg/ml to about 25 mg/ml, from about 1.2 mg/ml to about 25 mg/ml, from about 1.3 mg/ml to about 25 mg/ml, from about 1.4 mg/ml to about 25 mg/ml, from about 1.5 mg/ml to about 25 mg/ml, from about 1.6 mg/ml to about 25 mg/ml, from about 1.7 mg/ml to about 25 mg/ml, from about 0.5 mg/ml to about 24 mg/ml, from about 0.5 mg/ml to about 22 mg/ml, from about 0.5 mg/ml to about 20 mg/ml, from about 0.5 mg/ml to about 18 mg/ml, from about 0.5 mg/ml to about 15 mg/ml, from about 0.5 mg/ml to about 12 mg/ml, from about 0.5 mg/ml to about 10 mg/ml, from about 0.5 mg/ml to about 5 mg/ml, from about 0.5 mg/ml to about 2 mg/ml, from about 0.5 mg/ml to about 1.9 mg/ml, from about 0.5 mg/ml to about 1.8 mg/ml, from about 0.5 mg/ml to about 1.7 mg/ml, from about 0.5 mg/ml to about 1.6 mg/ml, from about 0.6 mg/ml to about 1.6 mg/ml, from about 0.7 mg/ml to about 1.6 mg/ml, from about 0.8 mg/ml to about 1.6 mg/ml, about 0.5 mg/ml, about 0.6 mg/ml, about 0.7 mg/ml, about 0.8 mg/ml, about 0.9 mg/ml, about 1.0 mg/ml, about 1.1 mg/ml, about 1.2 mg/ml, about 1.3 mg/ml, about 1.4 mg/ml, about 1.5 mg/ml, about 1.6 mg/ml, about 12 mg/ml, about 18 mg/ml, about 20 mg/ml, about 21.8 mg/ml, about 24 mg/ml, eic. In an exemplary embodiment, the cationic oil-in- water emulsion comprises from about 0.8 mg/ml to about 1.6 mg/ml DOTAP, such as 0.8 mg/ml, 1.2 mg/ml, 1.4 mg/ml or 1.6 mg/ml.
[0145] In certain embodiments, the cationic lipid is DC Cholesterol. The cationic oil- in-water emulsion may comprise DC Cholesterol at from about 0.1 mg/ml to about 5 mg/ml DC Cholesterol. For example, the cationic oil-in- water emulsion may comprise DC
Cholesterol from about 0.1 mg/ml to about 5 mg/ml, from about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5 mg/ml, from about 0.4 mg/ml to about 5 mg/ml, from about 0.5 mg/ml to about 5 mg/ml, from about 0.62 mg/ml to about 5 mg/ml, from about 1 mg/ml to about 5 mg/ml, from about 1.5 mg/ml to about 5 mg/ml, from about 2 mg/ml to about 5 mg/ml, from about 2.46 mg/ml to about 5 mg/ml, from about 3 mg/ml to about 5 mg/ml, from about 3.5 mg/ml to about 5 mg/ml, from about 4 mg/ml to about 5 mg/ml, from about 4.5 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to about 4.92 mg/ml, from about 0.1 mg/ml to about 4.5 mg/ml, from about 0.1 mg/ml to about 4 mg/ml, from about 0.1 mg/ml to about 3.5 mg/ml, from about 0.1 mg/ml to about 3 mg/ml, from about 0.1 mg/ml to about 2.46 mg/ml, from about 0.1 mg/ml to about 2 mg/ml, from about 0.1 mg/ml to about 1.5 mg/ml, from about 0.1 mg/ml to about 1 mg/ml, from about 0.1 mg/ml to about 0.62 mg/ml, about 0.15 mg/ml, about 0.3 mg/ml, about 0.6 mg/ml, about 0.62 mg/ml, about 0.9 mg/ml, about 1.2 mg/ml, about 2.46 mg/ml, about 4.92 mg/ml, eic. In an exemplary embodiment, the cationic oil-in- water emulsion comprises from about 0.62 mg/ml to about 4.92 mg/ml DC Cholesterol, such as 2.46 mg/ml.
[0146] In certain embodiments, the cationic lipid is DDA. The cationic oil-in-water emulsion may comprise from about 0.1 mg/ml to about 5 mg/ml DDA. For example, the cationic oil-in-water emulsion may comprise DDA at from about 0.1 mg/ml to about 5 mg/ml, from about 0.1 mg/ml to about 4.5 mg/ml, from about 0.1 mg/ml to about 4 mg/ml, from about 0.1 mg/ml to about 3.5 mg/ml, from about 0.1 mg/ml to about 3 mg/ml, from about 0.1 mg/ml to about 2.5 mg/ml, from about 0.1 mg/ml to about 2 mg/ml, from about 0.1 mg/ml to about 1.5 mg/ml, from about 0.1 mg/ml to about 1.45 mg/ml, from about 0.2 mg/ml to about 5 mg/ml, from about 0.3 mg/ml to about 5 mg/ml, from about 0.4 mg/ml to about 5 mg/ml, from about 0.5 mg/ml to about 5 mg/ml, from about 0.6 mg/ml to about 5 mg/ml, from about 0.73 mg/ml to about 5 mg/ml, from about 0.8 mg/ml to about 5 mg/ml, from about 0.9 mg/ml to about 5 mg/ml, from about 1.0 mg/ml to about 5 mg/ml, from about 1.2 mg/ml to about 5 mg/ml, from about 1.45 mg/ml to about 5 mg/ml, from about 2 mg/ml to about 5 mg/ml, from about 2.5 mg/ml to about 5 mg/ml, from about 3 mg/ml to about 5 mg/ml, from about 3.5 mg/ml to about 5 mg/ml, from about 4 mg/ml to about 5 mg/ml, from about 4.5 mg/ml to about 5 mg/ml, about 1.2 mg/ml, about 1.45 mg/ml, etc. Alternatively, the cationic oil-in-water emulsion may comprise DDA at about 20 mg/ml, about 21 mg/ml, about 21.5 mg/ml, about 21.6 mg/ml, about 25 mg/ml. In an exemplary embodiment, the cationic oil-in-water emulsion comprises from about 0.73 mg/ml to about 1.45 mg/ml DDA, such as 1.45 mg/ml.
[0147] Catheters or like devices may be used to deliver the self-replicating RNA molecules of the invention, as naked RNA or in combination with a delivery system, into a target organ or tissue. Suitable catheters are disclosed in, e.g. , U.S. Pat. Nos. 4,186,745; 5,397,307; 5,547,472; 5,674, 192; and 6, 129,705, all of which are incorporated herein by reference.
[0148] The present invention includes the use of suitable delivery systems, such as liposomes, polymer microparticles or submicron emulsion microparticles with encapsulated or adsorbed self-replicating RNA, to deliver a self-replicating RNA molecule that encodes an RSV-F polypeptide, for example, to elicit an immune response alone, or in combination with another macromolecule. The invention includes liposomes, microparticles and submicron emulsions with adsorbed and/or encapsulated self-replicating RNA molecules, and combinations thereof.
[0149] As demonstrated further in the Examples, the self-replicating RNA molecules associated with liposomes and submicron emulsion microparticles can be effectively delivered to the host cell, and can induce an immune response to the protein encoded by the self-replicating RNA.
Immunogenic compositions
[0150] The invention provides immunogenic compositions. The immunogenic compositions may include a single active immunogenic agent, or several immunogenic agents. For example, the immunogenic composition can comprise pre-fusion RSV F polypeptides or a combination of pre-fusion chimeric RSV F polypeptides. The
immunogenic composition can comprise a self-replicating RNA encoding a pre-fusion RSV- F polypeptide, and preferably also comprises a suitable delivery system, such as liposomes, polymeric microparticles, an oil-in-water emulsion and combinations thereof.
[0151] Immunogenic compositions of the invention may also comprise one or more immunoregulatory agents. Preferably, one or more of the immunoregulatory agents include one or more adjuvants, for example two, three, four or more adjuvants. The adjuvants may include a TH1 adjuvant and/or a TH2 adjuvant, further discussed below.
[0152] In another embodiment, an immunogenic composition of the invention comprises a polypeptide that displays an epitope present in a pre-fusion conformation of RSV-F glycoprotein.
[0153] In another embodiment, an immunogenic composition of the invention comprises one or more pre-fusion chimera proteins based on two different pre-fusion non- RSV (F proteins (e.g, metapneumo virus, parainfluenza, such asPIV5, NDV), in which both have the same RSV F neutralizing epitopes mutated on the protein surface.
[0154] The compositions of the invention are preferably suitable for administration to a mammalian subject, such as a human, and include one or more pharmaceutically acceptable carrier(s) and/or excipient(s), including adjuvants. A thorough discussion of such components is available in reference 29. Compositions will generally be in aqueous form. When the composition is an immunogenic composition, it will elicit an immune response when administered to a mammal, such as a human. The immunogenic composition can be used to prepare a vaccine formulation for immunizing a mammal.
[0155] The immunogenic compositions may include a single active immunogenic agent, or several immunogenic agents. For example, the pre-fusion RSV F protein can be full length or a ecto-domain polypeptide and can be in a single form (e.g., uncleaved monomer, cleaved monomer, uncleaved trimer, cleaved trimer) or in two or more forms (e.g., a mixture of uncleaved monomer and uncleaved trimer or a dynamic equilibrium between uncleaved monomer and uncleaved trimer). In addition, the compositions can contain a pre-fusion RSV F protein and one or more other RSV proteins (e.g., a G protein and/or an M protein) and/or it may be combined with immunogens from other pathogens.
[0156] The composition may include preservatives such as thiomersal or 2- phenoxyethanol. It is preferred, however, that the vaccine should be substantially free from (i.e. , less than 5μg/ml) mercurial material, e.g. , thiomersal-free. Immunogenic compositions containing no mercury are more preferred. Preservative-free immunogenic compositions are particularly preferred. [0157] To control tonicity, it is preferred to include a physiological salt, such as a sodium salt. Sodium chloride (NaCl) is preferred, which may be present at between 1 and 20 mg/ml. Other salts that may be present include potassium chloride, potassium dihydrogen phosphate, disodium phosphate dehydrate, magnesium chloride, calcium chloride, and the like.
[0158] Compositions will generally have an osmolality of between 200 mOsm/kg and 400 mOsm/kg, preferably between 240-360 mOsm/kg, and will more preferably fall within the range of 290-310 mOsm/kg.
[0159] Compositions may include one or more buffers. Typical buffers include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer
(particularly with an aluminum hydroxide adjuvant); or a citrate buffer. Buffers will typically be included in the 5-20mM range. The pH of a composition will generally be between 5.0 and 8.1, and more typically between 6.0 and 8.0, e.g. , between 6.5 and 7.5, or between 7.0 and 7.8. A process of the invention may therefore include a step of adjusting the pH of the bulk vaccine prior to packaging.
[0160] The composition is preferably sterile. The composition is preferably non-pyrogenic, e.g., containing <1 EU (endotoxin unit, a standard measure) per dose, and preferably <0.1 EU per dose. The composition is preferably gluten free. Human vaccines are typically administered in a dosage volume of about 0.5ml, although a half dose (i.e., about 0.25ml) may be administered to children.
Adjuvants
[0161] Compositions of the invention, that contain RSV-F polypeptides, or nucleic acids that encode RSV-F polypeptides, may also include one or more adjuvants, for example two, three, four or more adjuvants, which can function to enhance the immune responses (humoral and/or cellular) elicited in a patient who receives the composition. The adjuvants may include a TH1 adjuvant and/or a TH2 adjuvant. Adjuvants which may be used in compositions of the invention include, but are not limited to:
• Mineral-containing compositions. Mineral-containing compositions suitable for use as adjuvants in the invention include mineral salts, such as calcium salts and aluminum salts (or mixtures thereof). The invention includes mineral salts such as hydroxides (e.g. oxyhydroxides), phosphates (e.g. hydroxyphosphates, orthophosphates), sulphates, etc. , or mixtures of different mineral compounds, with the compounds taking any suitable form (e.g. gel, crystalline, amorphous, etc.), and with adsorption being preferred. Calcium salts include calcium phosphate (e.g., the "CAP" particles disclosed in ref. 38). Aluminum salts include hydroxides, phosphates, sulfates, and the like. The mineral containing compositions may also be formulated as a particle of metal salt (39). Aluminum salt adjuvants are described in more detail below.
Oil emulsion compositions (see in more detail below). Oil emulsion compositions suitable for use as adjuvants in the invention include squalene-water emulsions, such as MF59 (5% Squalene, 0.5% Tween 80 and 0.5% Span, formulated into submicron particles using a microfluidizer).
Cytokine-inducing agents (see in more detail below). Cytokine-inducing agents suitable for use in the invention include toll-like receptor 7 (TLR7) agonists (e.g. benzonaphthyridine compounds disclosed in WO 2009/111337.
Saponins (chapter 22 of ref. 74), which are a heterologous group of sterol glycosides and triterpenoid glycosides that are found in the bark, leaves, stems, roots and even flowers of a wide range of plant species. Saponin from the bark of the Quillaia saponaria Molina tree have been widely studied as adjuvants. Saponin can also be commercially obtained from Smilax ornata (sarsaprilla), Gypsophilla paniculata (brides veil), and Saponaria officianalis (soap root). Saponin adjuvant formulations include purified formulations, such as QS21, as well as lipid formulations, such as ISCOMs. QS21 is marketed as STIMULON (TM). Saponin compositions have been purified using HPLC and RP-HPLC. Specific purified fractions using these techniques have been identified, including QS7, QS17, QS18, QS21, QH-A, QH-B and QH-C. Preferably, the saponin is QS21. A method of production of QS21 is disclosed in ref. 40. Saponin formulations may also comprise a sterol, such as cholesterol (41). Combinations of saponins and cholesterols can be used to form unique particles called immunostimulating complexes (ISCOMs) (chapter 23 of ref. 74). ISCOMs typically also include a phospholipid such as phosphatidylethanolamine or phosphatidylcholine. Any known saponin can be used in ISCOMs. Preferably, the ISCOM includes one or more of QuilA, QHA & QHC. ISCOMs are further described in refs. 41-43. Optionally, the ISCOMS may be devoid of additional detergent (44). A review of the development of saponin based adjuvants can be found in refs. 45 & 46.
Fatty adjuvants (see in more detail below), including oil-in-water emulsions, modified natural lipid As derived from enterobacterial lipopolysaccharides, phospholipid compounds (such as the synthetic phospholipid dimer, E6020) and the like. Bacterial ADP-ribosylating toxins (e.g., the E. coli heat labile enterotoxin "LT", cholera toxin "CT", or pertussis toxin "PT") and detoxified derivatives thereof, such as the mutant toxins known as LT-K63 and LT-R72 (47). The use of detoxified ADP- ribosylating toxins as mucosal adjuvants is described in ref. 48 and as parenteral adjuvants in ref. 49.
Bioadhesives and mucoadhesives, such as esterified hyaluronic acid microspheres (50) or chitosan and its derivatives (51).
Microparticles (i.e., a particle of -100 nm to -150 μιη in diameter, more preferably -200 nm to -30 μιη in diameter, or -500 nm to -10 μιη in diameter) formed from materials that are biodegradable and non-toxic (e.g., a poly(a-hydroxy acid), a polyhydroxybutyric acid, a polyorthoester, a polyanhydride, a polycaprolactone, and the like), with poly(lactide-co-glycolide) being preferred, optionally treated to have a negatively-charged surface (e.g., with SDS) or a positively-charged surface (e.g., with a cationic detergent, such as CTAB).
Liposomes (Chapters 13 & 14 of ref. 74). Examples of liposome formulations suitable for use as adjuvants are described in refs. 52-54.
Polyoxyethylene ethers and polyoxyethylene esters (55). Such formulations further include polyoxyethylene sorbitan ester surfactants in combination with an octoxynol (56) as well as polyoxyethylene alkyl ethers or ester surfactants in combination with at least one additional non-ionic surfactant such as an octoxynol (57). Preferred polyoxyethylene ethers are selected from the following group: polyoxyethylene-9- lauryl ether (laureth 9), polyoxyethylene-9-steoryl ether, polyoxytheylene-8-steoryl ether, polyoxyethylene-4-lauryl ether, polyoxyethylene-35-lauryl ether, and polyoxyethylene-23-lauryl ether.
Muramyl peptides, such as N-acetylmuramyl-L-threonyl-D-isoglutamine ("thr- MDP"), N-acetyl-normuramyl-L-alanyl-D-isoglutamine (nor-MDP), N- acetylglucsaminyl-N-acetylmuramyl-L-Al-D-isoglu-L-Ala-dipalmitoxy propylamide ("DTP-DPP", or "Theramide™), N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L- alanine-2-(l'-2'dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine ("MTP- PE").
An outer membrane protein proteosome preparation prepared from a first Gram- negative bacterium in combination with a liposaccharide preparation derived from a second Gram-negative bacterium, wherein the outer membrane protein proteosome and liposaccharide preparations form a stable non-covalent adjuvant complex. Such complexes include "IVX-908", a complex comprised of Neisseria meningitidis outer membrane and lipopolysaccharides.
• A polyoxidonium polymer (58, 59) or other N-oxidized polyethylene-piperazine derivative.
• Methyl inosine 5 '-monophosphate ("MIMP") (60).
• A polyhydroxlated pyrrolizidine compound (61), such as one having formula: where R is selected from the group comprising hydrogen, straight or branched, unsubstituted or substituted, saturated or unsaturated acyl, alkyl {e.g., cycloalkyl), alkenyl, alkynyl and aryl groups, or a pharmaceutically acceptable salt or derivative thereof. Examples include, but are not limited to: casuarine, casuarine-6-a-D- glucopyranose, 3-e/?/-casuarine, 7-ep -casuarine, 3,7-die/?/-casuarine, and the like
• A CD Id ligand, such as an a-glycosylceramide (62-69) {e.g., a-galactosylceramide), phytosphingosine-containing a-glycosylceramides, OCH, KRN7000 [(2S,3S,4R)-1- 0-(a-D-galactopyranosyl)-2-(N-hexacosanoylamino)-l,3,4-octadecanetriol],
CRONY-101, 3"-0-sulfo-galactosylceramide, etc.
• A gamma inulin (70) or derivative thereof, such as algammulin.
• Virosomes and virus-like particles (VLPs). These structures generally contain one or more proteins from a virus optionally combined or formulated with a phospholipid. They are generally non-pathogenic, non-replicating and generally do not contain any of the native viral genome. The viral proteins may be recombinantly produced or isolated from whole viruses. These viral proteins suitable for use in virosomes or VLPs include proteins derived from influenza virus (such as HA or NA), Hepatitis B virus (such as core or capsid proteins), Hepatitis E virus, measles virus, Sindbis virus, Rotavirus, Foot-and- Mouth Disease virus, Retrovirus, Norwalk virus, human Papilloma virus, HIV, RNA- phages, Q6-phage (such as coat proteins), GA-phage, fr-phage, AP205 phage, and Ty (such as retrotransposon Ty protein pi).
[0162] These and other adjuvant-active substances are discussed in more detail in references 74 & 75.
[0163] Compositions may include two, three, four or more adjuvants. For example, compositions of the invention may advantageously include both an oil-in- water emulsion and a cytokine-inducing agent, or both a mineral-containing composition and a cytokine-inducing agent, or two oil-in-water emulsion adjuvants, or two benzonaphthyridine compounds, etc.
[0164] Antigens and adjuvants in a composition will typically be in admixture. Oil emulsion adjuvants
[0165] Oil emulsion compositions suitable for use as adjuvants in the invention include squalene-water emulsions, such as MF59 (5% Squalene, 0.5% Tween 80, and 0.5% Span 85, formulated into submicron particles using a microfluidizer). Complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IF A) may also be used.
[0166] Various oil-in- water emulsions are known, and they typically include at least one oil and at least one surfactant, with the oil(s) and surfactant(s) being biodegradable (metabolizable) and biocompatible. The oil droplets in the emulsion are generally less than 5 μιη in diameter, and may even have a sub-micron diameter, with these small sizes being achieved with a microfluidizer to provide stable emulsions. Droplets with a size less than 220 nm are preferred as they can be subjected to filter sterilization.
[0167] The invention can be used with oils such as those from an animal (such as fish) or vegetable source. Sources for vegetable oils include nuts, seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil, the most commonly available, exemplify the nut oils. Jojoba oil can be used, e.g., obtained from the jojoba bean. Seed oils include safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like. In the grain group, corn oil is the most readily available, but the oil of other cereal grains such as wheat, oats, rye, rice, teff, triticale and the like may also be used. 6-10 carbon fatty acid esters of glycerol and 1 ,2-propanediol, while not occurring naturally in seed oils, may be prepared by hydrolysis, separation and esterification of the appropriate materials starting from the nut and seed oils. Fats and oils from mammalian milk are metabolizable and may therefore be used in the practice of this invention. The procedures for separation, purification, saponification and other means necessary for obtaining pure oils from animal sources are well known in the art. Most fish contain metabolizable oils which may be readily recovered. For example, cod liver oil, shark liver oils, and whale oil such as spermaceti exemplify several of the fish oils which may be used herein. A number of branched chain oils are synthesized biochemically in 5- carbon isoprene units and are generally referred to as terpenoids. Shark liver oil contains a branched, unsaturated terpenoid known as squalene, 2,6,10,15, 19, 23-hexamethyl- 2,6,10,14,18,22-tetracosahexaene, which is particularly preferred herein. Squalane, the saturated analog to squalene, is also preferred oil. Fish oils, including squalene and squalane, are readily available from commercial sources or may be obtained by methods known in the art. Other preferred oils are the tocopherols (see below). Mixtures of oils can be used. [0168] Surfactants can be classified by their 'HLB' (hydrophile/lipophile balance). Preferred surfactants of the invention have a HLB of at least 10, preferably at least 15, and more preferably at least 16. The invention can be used with surfactants including, but not limited to: the polyoxyethylene sorbitan esters surfactants (commonly referred to as the Tweens), especially polysorbate 20 and polysorbate 80; copolymers of ethylene oxide (EO), propylene oxide (PO), and/or butylene oxide (BO), sold under the DOWFAX (TM) tradename, such as linear EO/PO block copolymers; octoxynols, which can vary in the number of repeating ethoxy (oxy-l,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, or t-octylphenoxypolyethoxyethanol) being of particular interest;
(octylphenoxy)polyethoxyethanol (IGEPAL CA-630/NP-40); phospholipids such as phosphatidylcholine (lecithin); nonylphenol ethoxylates, such as the TERGITOL (TM) NP series; polyoxyethylene fatty ethers derived from lauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants), such as triethyleneglycol monolauryl ether (Brij 30); and sorbitan esters (commonly known as the SPANs), such as sorbitan trioleate (Span 85) and sorbitan monolaurate. Non-ionic surfactants are preferred. Preferred surfactants for including in the emulsion are TWEEN 80 (TM) (polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate), lecithin and Triton X-100.
[0169] Mixtures of surfactants can be used e.g., TWEEN 80 (TM)/Span 85 mixtures. A combination of a polyoxyethylene sorbitan ester such as polyoxyethylene sorbitan monooleate (TWEEN 80 (TM)) and an octoxynol such as t-octylphenoxypolyethoxyethanol (Triton X-100) is also suitable. Another useful combination comprises laureth 9 plus a polyoxyethylene sorbitan ester and/or an octoxynol.
[0170] Preferred amounts of surfactants (% by weight) are: polyoxyethylene sorbitan esters (such as TWEEN 80 (TM)) 0.01 to 1 %, in particular about 0.1 %; octyl- or
nonylphenoxy polyoxyethanols (such as Triton X-100, or other detergents in the Triton series) 0.001 to 0.1 %, in particular 0.005 to 0.02%; polyoxyethylene ethers (such as laureth 9) 0.1 to 20 %, preferably 0.1 to 10 % and in particular 0.1 to 1 % or about 0.5%.
[0171] Specific oil-in-water emulsion adjuvants useful with the invention include, but are not limited to:
• A submicron emulsion of squalene, TWEEN 80 (TM), and Span 85. The composition of the emulsion by volume can be about 5% squalene, about 0.5% polysorbate 80 and about 0.5% Span 85. In weight terms, these ratios become 4.3% squalene, 0.5% polysorbate 80 and 0.48% Span 85. This adjuvant is known as 'MF59' (71-73), as described in more detail in Chapter 10 of ref. 74 and chapter 12 of ref. 75. The MF59 emulsion advantageously includes citrate ions, e.g., lOmM sodium citrate buffer.
An emulsion of squalene, a tocopherol, and TWEEN 80 (TM). The emulsion may include phosphate buffered saline. It may also include Span 85 (e.g., at 1 %) and/or lecithin. These emulsions may have from 2 to 10% squalene, from 2 to 10% tocopherol and from 0.3 to 3% TWEEN 80 (TM), and the weight ratio of squalene tocopherol is preferably <1 as this provides a more stable emulsion. Squalene and TWEEN 80 (TM) may be present volume ratio of about 5:2. One such emulsion can be made by dissolving TWEEN 80 (TM) in PBS to give a 2% solution, then mixing 90ml of this solution with a mixture of (5g of DL-a-tocopherol and 5ml squalene), then microfluidizing the mixture. The resulting emulsion may have submicron oil droplets, e.g., with an average diameter of between 100 and 250nm, preferably about 180nm.
An emulsion of squalene, a tocopherol, and a Triton detergent (e.g., Triton X-100). The emulsion may also include a 3d-MPL (see below). The emulsion may contain a phosphate buffer.
An emulsion comprising a polysorbate (e.g., polysorbate 80), a Triton detergent (e.g., Triton X-100) and a tocopherol (e.g., an a-tocopherol succinate). The emulsion may include these three components at a mass ratio of about 75: 11 : 10 (e.g., 750 μg/ml polysorbate 80, 110 μg/ml Triton X-100 and 100 μg/ml α-tocopherol succinate), and these concentrations should include any contribution of these components from antigens. The emulsion may also include squalene. The emulsion may also include a 3d-MPL (see below). The aqueous phase may contain a phosphate buffer.
An emulsion of squalane, polysorbate 80 and poloxamer 401 ("PLURONIC (TM) L121"). The emulsion can be formulated in phosphate buffered saline, pH 7.4. This emulsion is a useful delivery vehicle for muramyl dipeptides, and has been used with threonyl-MDP in the "SAF-1" adjuvant (76) (0.05-1 % Thr-MDP, 5% squalane, 2.5% Pluronic L121 and 0.2% polysorbate 80). It can also be used without the Thr-MDP, as in the "AF' adjuvant (77) (5% squalane, 1.25% Pluronic L121 and 0.2% polysorbate 80). Microfluidization is preferred.
An emulsion comprising squalene, an aqueous solvent, a polyoxyethylene alkyl ether hydrophilic nonionic surfactant (e.g. polyoxyethylene (12) cetostearyl ether) and a hydrophobic nonionic surfactant (e.g. a sorbitan ester or mannide ester, such as sorbitan monoleate or 'Span 80')· The emulsion is preferably thermoreversible and/or has at least 90% of the oil droplets (by volume) with a size less than 200 nm. The emulsion may also include one or more of: alditol; a cryoprotective agent (e.g. a sugar, such as dodecylmaltoside and/or sucrose); and/or an alky lpoly glycoside. Such emulsions may be lyophilized.
• An emulsion having from 0.5-50% of an oil, 0.1-10% of a phospholipid, and 0.05-5% of a non- ionic surfactant. As described in reference 78, preferred phospholipid components are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cardiolipin. Submicron droplet sizes are advantageous.
• A submicron oil-in-water emulsion of a non-metabolizable oil (such as light mineral oil) and at least one surfactant (such as lecithin, TWEEN 80 (TM) or Span 80). Additives may be included, such as QuilA saponin, cholesterol, a saponin-lipophile conjugate (such as GPI-0100, described in reference 79, produced by addition of aliphatic amine to desacylsaponin via the carboxyl group of glucuronic acid), dimethyidioctadecylammonium bromide and/or N,N-dioctadecyl-N,N-bis (2- hydroxyethyl)propanediamine.
• An emulsion comprising a mineral oil, a non-ionic lipophilic ethoxylated fatty alcohol, and a non- ionic hydrophilic surfactant (e.g. an ethoxylated fatty alcohol and/or poly oxye thy lene-polyoxypropylene block copolymer).
• An emulsion comprising a mineral oil, a non-ionic hydrophilic ethoxylated fatty alcohol, and a non-ionic lipophilic surfactant (e.g. an ethoxylated fatty alcohol and/or poly oxye thy lene-polyoxypropylene block copolymer).
• An emulsion in which a saponin (e.g., QuilA or QS21) and a sterol (e.g., a cholesterol) are associated as helical micelles (80).
[0172] The emulsions may be mixed with antigen extemporaneously, at the time of delivery. Thus the adjuvant and antigen may be kept separately in a packaged or distributed vaccine, ready for final formulation at the time of use. The antigen will generally be in an aqueous form, such that the vaccine is finally prepared by mixing two liquids. The volume ratio of the two liquids for mixing can vary (e.g., between 5: 1 and 1 :5) but is generally about 1 : 1.
Cytokine-inducing agents
[0173] Cytokine-inducing agents for inclusion in compositions of the invention are able, when administered to a patient, to elicit the immune system to release cytokines, including interferons and interleukins. Preferred agents can elicit the release of one or more of: interferon-γ; interleukin-1 ; interleukin-2; interleukin-12; TNF-a; TNF-β; and GM-CSF. Preferred agents elicit the release of cytokines associated with a Thl-type immune response, e.g., interferon-γ, TNF-a, interleukin-2. Stimulation of both interferon-γ and interleukin-2 is preferred.
[0174] As a result of receiving a composition of the invention, therefore, a patient will have T cells that, when stimulated with a RSV F protein, will release the desired cytokine(s) in an antigen-specific manner. For example, T cells purified from their blood will release γ-interferon when exposed in vitro to F protein. Methods for measuring such responses in peripheral blood mononuclear cells (PBMC) are known in the art, and include ELISA, ELISPOT, flow-cytometry and real-time PCR. For example, reference 81 reports a study in which antigen- specific T cell-mediated immune responses against tetanus toxoid, specifically γ-interferon responses, were monitored, and found that ELISPOT was the most sensitive method to discriminate antigen-specific TT-induced responses from spontaneous responses, but that intracytoplasmic cytokine detection by flow cytometry was the most efficient method to detect re-stimulating effects.
[0175] Suitable cytokine-inducing agents include, but are not limited to:
• An immunostimulatory oligonucleotide, such as one containing a CpG motif (a dinucleotide sequence containing an unmethylated cytosine linked by a phosphate bond to a guanosine), or a double-stranded RNA, or an oligonucleotide containing a palindromic sequence, or an oligonucleotide containing a poly(dG) sequence.
• 3-O-deacylated monophosphoryl lipid A ('3dMPL' , also known as 'MPL (TM)') (82- 85).
• An imidazoquinoline compound, such as IMIQUIMOD (TM) ("R-837") (86, 87), RESIQUIMOD (TM) ("R-848") (88), and their analogs; and salts thereof {e.g., the hydrochloride salts). Further details about immunostimulatory imidazoquinolines can be found in references 89 to 93.
• A benzonaphthyridine compound, such as: (a) a compound having the formula: wherein:
R4 is selected from H, halogen, -C(0)OR7, -C(0)R7, -C(0)N(RnR12), -N(RnR12), -N(R9)2, -NHN(R9)2, -SR7, -(CH2)nOR7, -(CH2)nR7,
-LR8, -LR10, -OLR8, -OLR10, Ci-C6alkyl, Ci-C6heteroalkyl,
Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne, Ci-C6alkoxy, Ci-Cehaloalkoxy, aryl, heteroaryl, C3-Cscycloalkyl, and C3-C8heterocycloalkyl, wherein the Ci-C6alkyl, Ci-C6heteroalkyl, C\- C6haloalkyl, C2-Csalkene, C2-Csalkyne, Ci-C6alkoxy,
Ci-C6haloalkoxy, aryl, heteroaryl, C3-Cscycloalkyl, and
C3-Csheterocycloalkyl groups of R4 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, -N02, -R7, - OR8, -C(0)R8, -OC(0)R8, -C(0)OR8, -N(R9)2, -P(0)(OR8)2, - OP(0)(OR8)2, -P(O)(OR10)2,
-OP(O)(OR10)2, -C(0)N(R9)2, -S(0)2R8, -S(0)R8, -S(0)2N(R9)2, and - NR9S(0)2R8;
each L is independently selected from a bond, -(0(CH2)m)r, Ci-C6alkyl,
C2-C6alkenylene and C2-C6alkynylene, wherein the Ci-C6alkyl,
C2-C6alkenylene and C2-C6alkynylene of L are each optionally substituted with 1 to 4 substituents independently selected from halogen, -R8, -OR8, - N(R9)2, -P(0)(OR8)2, -OP(0)(OR8)2,
-P(O)(OR10)2, and -OP(O)(OR10)2;
R7 is selected from H, Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl, wherein the Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl groups of R7 are each optionally substituted with 1 to 3 R13 groups;
each R8 is independently selected from H, -CH(R10)2, Ci-Csalkyl,
C2-C8alkene, C2-Csalkyne, Ci-C6haloalkyl, Ci-C6alkoxy,
Ci-C6heteroalkyl, C3-Cscycloalkyl, C2-Csheterocycloalkyl,
Ci-C6hydroxyalkyl and Ci-C6haloalkoxy, wherein the Ci-Csalkyl, C2- Csalkene, C2-Csalkyne, Ci-C6heteroalkyl, Ci-C6haloalkyl,
Ci-C6alkoxy, C3-Cscycloalkyl, C2-C8heterocycloalkyl,
Ci-C6hydroxyalkyl and Ci-C6haloalkoxy groups of R8 are each optionally substituted with 1 to 3 substituents independently selected from -CN, R11, -OR11, -SR11, -C(0)Rn, -OC(0)Rn,
-C(0)N(R9)2, -C(0)ORn, -NR9C(0)Rn, -NR9R10, -NRnR12, -N(R9)2, - OR9, -OR10, -C(0)NRnR12, -C(0)NRnOH, -S(0)2RH,
-S(0)Rn, -S(0)2NRnR12, -NRnS(0)2Rn , -P(0)(ORn)2, and -OP(0)(ORn)2;
ch R9 is independently selected from H, -C(0)R8, -C(0)OR8, -C(0)R10,
-C(0)OR10, -S(0)2R10, -Ci-C6 alkyl, Ci-C6 heteroalkyl and C3-C6 cycloalkyl, or each R9 is independently a Ci-C6alkyl that together with N they are attached to form a C3-Csheterocycloalkyl, wherein the C3- Csheterocycloalkyl ring optionally contains an additional heteroatom selected from N, O and S, and wherein the Ci-C6 alkyl, Ci-C6 heteroalkyl, C3-C6 cycloalkyl, or
C3-Csheterocycloalkyl groups of R9 are each optionally substituted with 1 to 3 substituents independently selected from
-CN, R11, -OR11, -SR11, -C(0)Rn, -OC(0)Rn, -C(0)ORn,
-NRnR12, -C(0)NRnR12, -C(0)NRnOH, -S(0)2Rn, -S(0)Rn,
-S(0)2NRnR12, -NR11S(0)2R11, -P(0)(ORn)2, and
-OP(0)(ORn)2;
ch R10 is independently selected from aryl, C3-Cscycloalkyl,
C3-Csheterocycloalkyl and heteroaryl, wherein the aryl,
C3-C8cycloalkyl, C3-Csheterocycloalkyl and heteroaryl groups are optionally substituted with 1 to 3 substituents selected from halogen, -R8, - OR8, -LR9, -LOR9, -N(R9)2, -NR9C(0)R8,
-NR9C02R8, -C02R8, -C(0)R8 and -C(0)N(R9)2;
1 and R12 are independently selected from H, Ci-C6alkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl,
C3-C8cycloalkyl, and C3-Csheterocycloalkyl, wherein the
Ci-C6alkyl, Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl, C3- Cscycloalkyl, and C3-Csheterocycloalkyl groups of R11 and R12 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, R8, -OR8, -C(0)R8,
OC(0)R8, -C(0)OR8, -N(R9)2, -NR8C(0)R8, -NR8C(0)OR8,
-C(0)N(R9)2, Cs-Csheterocycloalkyl, -S(0)2R8, -S(0)2N(R9)2,
-NR9S(0)2R8, Ci-C6haloalkyl and Ci-C6haloalkoxy;
R11 and R12 are each independently Ci-C6alkyl and taken together with the N atom to which they are attached form an optionally substituted C3- Csheterocycloalkyl ring optionally containing an additional heteroatom selected from N, O and S; each R13 is independently selected from halogen, -CN, -LR9, -LOR9,
-OLR9, -LR10, -LOR10, -OLR10, -LR8, -LOR8, -OLR8, -LSR8, -LSR10, -LC(0)R8, -OLC(0)R8, -LC(0)OR8, -LC(0)R10,
-LOC(0)OR8, -LC(0)NR9Rn, -LC(0)NR9R8, -LN(R9)2,
-LNR9R8, -LNR9R10, -LC(0)N(R9)2, -LS(0)2R8, -LS(0)R8,
-LC(0)NR8OH, -LNR9C(0)R8, -LNR9C(0)OR8, -LS(0)2N(R9)2, - OLS(0)2N(R9)2, -LNR9S(0)2R8, -LC(0)NR9LN(R9)2,
-LP(0)(OR8)2, -LOP(0)(OR8)2, -LP(O)(OR10)2 and
-OLP(O)(OR10)2;
each RA is independently selected from -R8, -R7, -OR7, -OR8, -R10,
-OR10, -SR8, -NO2, -CN, -N(R9)2, -NR9C(0)R8, -NR9C(S)R8, -NR9C(0)N(R9)2, -NR9C(S)N(R9)2, -NR9C02R8,
-NR9NR9C(0)R8, -NR9NR9C(0)N(R9)2, -NR9NR9C02R8,
-C(0)C(0)R8, -C(0)CH2C(0)R8, -C02R8, -(CH2)nC02R8,
-C(0)R8, -C(S)R8, -C(0)N(R9)2, -C(S)N(R9)2, -OC(0)N(R9)2, -OC(0)R8, -C(0)N(OR8)R8, -C(NOR8)R8, -S(0)2R8, -S(0)3R8, -S02N(R9)2, -S(0)R8, -NR9S02N(R9)2, -NR9S02R8, -P(0)(OR8)2, - OP(0)(OR8)2, -P(O)(OR10)2, -OP(O)(OR10)2, -N(OR8)R8,
-CH=CHC02R8, -C(=NH)-N(R9)2, and -(CH2)nNHC(0)R8; or two adjacent RA substituents on Ring A form a 5-6 membered ring that contains up to two heteroatoms as ring members;
n is, independently at each occurrence, 0, 1, 2, 3, 4, 5, 6, 7 or 8;
each m is independently selected from 1, 2, 3, 4, 5 and 6, and
t is 1, 2, 3, 4, 5, 6, 7 or 8; (b) a compound having the formula:
wherein:
R4 is selected from H, halogen, -C(0)OR7, -C(0)R7, -C(0)N(RnR12),
-N(RnR12), -N(R9)2, -NHN(R9)2, -SR7, -(CH2)nOR7, -(CH2)nR7, -LR8, -LR10, -OLR8, -OLR10, Ci-C6alkyl, Ci-C6heteroalkyl,
Ci-Cehaloalkyl, C2-Csalkene, C2-Csalkyne, Ci-C6alkoxy, Ci-C6haloalkoxy, aryl, heteroaryl, C3-Cscycloalkyl, and C3- Csheterocycloalkyl, wherein the Ci-C6alkyl, Ci-C6heteroalkyl, d- Cehaloalkyl, C2-Csalkene, C2-Csalkyne, Ci-C6alkoxy,
Ci-C6haloalkoxy, aryl, heteroaryl, C3-Cscycloalkyl, and
C3-Csheterocycloalkyl groups of R4 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, -N02, -R7, - OR8, -C(0)R8, -OC(0)R8, -C(0)OR8, -N(R9)2, -P(0)(OR8)2, - OP(0)(OR8)2, -P(O)(OR10)2,
-OP(O)(OR10)2, -C(0)N(R9)2, -S(0)2R8, -S(0)R8,
-S(0)2N(R9)2, and -NR9S(0)2R8;
each L is independently selected from a bond, -(0(CH2)m)r, Ci-C6alkyl, C2- C6alkenylene and C2-C6alkynylene, wherein the Ci-C6alkyl, C2- C6alkenylene and C2-C6alkynylene of L are each optionally substituted with 1 to 4 substituents independently selected from halogen, -R8, -OR8, - N(R9)2, -P(0)(OR8)2, -OP(0)(OR8)2,
-P(O)(OR10)2, and -OP(O)(OR10)2;
R7 is selected from H, Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl, wherein the Ci-C6alkyl, aryl, heteroaryl, C3-Cscycloalkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, C2-Csalkene, C2-Csalkyne,
Ci-C6alkoxy, Ci-C6haloalkoxy, and C3-Csheterocycloalkyl groups of R7 are each optionally substituted with 1 to 3 R13 groups;
each R 8 is independently selected from H, -CH(R 10 )2, Ci-Csalkyl,
C2-C8alkene, C2-Csalkyne, Ci-C6haloalkyl, Ci-C6alkoxy,
Ci-C6heteroalkyl, C3-Cscycloalkyl, C2-Csheterocycloalkyl,
Ci-C6hydroxyalkyl and Ci-C6haloalkoxy, wherein the Ci-Csalkyl, C2- Csalkene, C2-Csalkyne, Ci-C6heteroalkyl, Ci-C6haloalkyl,
Ci-C6alkoxy, C3-Cscycloalkyl, C2-C8heterocycloalkyl,
Ci-C6hydroxyalkyl and Ci-C6haloalkoxy groups of R8 are each optionally substituted with 1 to 3 substituents independently selected from -CN, R11, -OR11, -SR11, -C(0)Rn, -OC(0)Rn,
-C(0)N(R9)2, -C(0)ORn, -NR9C(0)Rn, -NR9R10, -NRnR12, -N(R9)2, -OR9, -OR10, -C(0)NRnR12, -C(0)NRnOH, -S(0)2Rn, - S(0)Rn, -S(0)2NRnR12, -NR^CO^R11, -P(0)(ORn)2, and
-OP(0)(ORn)2;
ch R9 is independently selected from H, -C(0)R8, -C(0)OR8, -C(0)R10, - C(0)OR10, -S(0)2R10, -Ci-C6 alkyl, Ci-C6 heteroalkyl and C3-C6 cycloalkyl, or each R9 is independently a Ci-C6alkyl that together with N they are attached to form a C3-Csheterocycloalkyl, wherein the C3- Csheterocycloalkyl ring optionally contains an additional heteroatom selected from N, O and S, and wherein the Ci-C6 alkyl, Ci-C6 heteroalkyl, C3-C6 cycloalkyl, or
C3-Csheterocycloalkyl groups of R9 are each optionally substituted with 1 to 3 substituents independently selected from
-CN, R11, -OR11, -SR11, -C(0)Rn, -OC(0)Rn, -C(0)ORn,
-NRnR12, -C(0)NRnR12, -C(0)NRnOH, -S(0)2Rn, -S(0)Rn,
-S(0)2NRnR12, -NR11S(0)2R11, -P(0)(ORn)2, and
-OP(0)(ORn)2;
ch R10 is independently selected from aryl, C3-Cscycloalkyl,
C3-Csheterocycloalkyl and heteroaryl, wherein the aryl,
C3-C8cycloalkyl, C3-Csheterocycloalkyl and heteroaryl groups are optionally substituted with 1 to 3 substituents selected from halogen, -R8, - OR8, -LR9, -LOR9, -N(R9)2, -NR9C(0)R8,
-NR9C02R8, -C02R8, -C(0)R8 and -C(0)N(R9)2;
1 and R12 are independently selected from H, Ci-C6alkyl,
Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl,
C3-C8cycloalkyl, and C3-Csheterocycloalkyl, wherein the
Ci-C6alkyl, Ci-C6heteroalkyl, Ci-C6haloalkyl, aryl, heteroaryl, C3- Cscycloalkyl, and C3-Csheterocycloalkyl groups of R11 and R12 are each optionally substituted with 1 to 3 substituents independently selected from halogen, -CN, R8, -OR8, -C(0)R8,
OC(0)R8, -C(0)OR8, -N(R9)2, -NR8C(0)R8, -NR8C(0)OR8,
-C(0)N(R9)2, C3-C8heterocycloalkyl, -S(0)2R8, -S(0)2N(R9)2,
-NR9S(0)2R8, Ci-C6haloalkyl and Ci-C6haloalkoxy;
R11 and R12 are each independently Ci-C6alkyl and taken together with the N atom to which they are attached form an optionally substituted C3- Csheterocycloalkyl ring optionally containing an additional heteroatom selected from N, O and S;
each R13 is independently selected from halogen, -CN, -LR9, -LOR9, -OLR9, -LR10, -LOR10, -OLR10, -LR8, -LOR8, -OLR8, -LSR8,
-LSR10, -LC(0)R8, -OLC(0)R8, -LC(0)OR8, -LC(0)R10, -LOC(0)OR8, -LC(0)NR9Rn, -LC(0)NR9R8, -LN(R9)2, -LNR9R8, -LNR9R10, -LC(0)N(R9)2, -LS(0)2R8, -LS(0)R8,
-LC(0)NR8OH, -LNR9C(0)R8, -LNR9C(0)OR8,
LS(0)2N(R9)2, -OLS(0)2N(R9)2, -LNR9S(0)2R8,
-LC(0)NR9LN(R9)2, -LP(0)(OR8)2, -LOP(0)(OR8)2,
-LP(O)(OR10)2 and -OLP(O)(OR10)2;
each RA is independently selected from -R8, -R7, -OR7, -OR8, -R10,
-OR10, -SR8, -N02, -CN, -N(R9)2, -NR9C(0)R8, -NR9C(S)R8,
-NR9C(0)N(R9)2, -NR9C(S)N(R9)2, -NR9C02R8,
-NR9NR9C(0)R8, -NR9NR9C(0)N(R9)2, -NR9NR9C02R8, -C(0)C(0)R8, -C(0)CH2C(0)R8, -C02R8, -(CH2)nC02R8, -C(0)R8, -C(S)R8, -C(0)N(R9)2, -C(S)N(R9)2, -OC(0)N(R9)2,
-OC(0)R8, -C(0)N(OR8)R8, -C(NOR8)R8, -S(0)2R8, -S(0)3R8,
-S02N(R9)2, -S(0)R8, -NR9S02N(R9)2, -NR9S02R8, -P(0)(OR8)2, - OP(0)(OR8)2, -P(O)(OR10)2, -OP(O)(OR10)2, -N(OR8)R8, -CH=CHC02R8, -C(=NH)-N(R9)2, and -(CH2)nNHC(0)R8;
n is, independently at each occurrence, 0, 1, 2, 3, 4, 5, 6, 7 or 8;
each m is independently selected from 1, 2, 3, 4, 5 and 6, and
t is 1, 2, 3, 4, 5, 6, 7 or 8; or (c) a pharmaceutically acceptable salt of any of (a) or (b).
[0176] Other benzonaphthyridine compounds, and methods of making
benzonaphthyridine compounds, are described in WO 2009/111337. A benzonaphthyridine compound, or a salt thereof, can be used on its own, or in combination with one or more further compounds. For example, a benzonaphthyridine compound can be used in combination with an oil-in-water emulsion or a mineral-containing composition. In a particular embodiment, a benzonaphthyridine compound is used in combination with an oil- in-water emulsion (e.g. a squalene-water emulsion, such as MF59) or a mineral-containing composition (e.g., a mineral said such as an aluminum salt or a calcium salt).
• A thiosemicarbazone compound, such as those disclosed in reference 94. Methods of formulating, manufacturing, and screening for active compounds are also described in reference 94. The thiosemicarbazones are particularly effective in the stimulation of human peripheral blood mononuclear cells for the production of cytokines, such as TNF-a.
A tryptanthrin compound, such as those disclosed in reference 95. Methods of formulating, manufacturing, and screening for active compounds are also described in reference 95. The thiosemicarbazones are particularly effective in the stimulation of human peripheral blood mononuclear cells for the production of cytokines, such as TNF-a.
A nucleoside analog, such as: (a) Isatorabine (ANA-245; 7-thia-8-oxoguanosine): and prodrugs thereof; (b) ANA975; (c) ANA-025-1; (d) ANA380; (e) the compounds disclosed in references 96 to 98; (f) a compound having the formula: wherein:
Ri and R2 are each independently H, halo, -NRaRb, -OH, Ci_6 alkoxy, substituted Ci_6 alkoxy, heterocyclyl, substituted heterocyclyl, C6-io aryl, substituted C6-io aryl, Ci_6 alkyl, or substituted Ci_6 alkyl;
R3 is absent, H, Ci_6 alkyl, substituted Ci_6 alkyl, C6-io aryl, substituted C6-io aryl, heterocyclyl, or substituted heterocyclyl;
R4 and R5 are each independently H, halo, heterocyclyl, substituted heterocyclyl, -C(0)-Rd, Ci_6 alkyl, substituted Ci_6 alkyl, or bound together to form a 5 membered ring as in R4_s:
R4-5 the binding being achieved at the bonds indicated by a Xi and X2 are each independently N, C, O, or S;
R8 is H, halo, -OH, Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, -OH, -NRaRb, - (CH2)n-0-Rc, -0-(d_6 alkyl), -S(0)pRe, or -C(0)-Rd;
R9 is H, Ci-6 alkyl, substituted Ci_6 alkyl, heterocyclyl, substituted heterocyclyl or R¾, wherein Rga is:
Figure imgf000064_0001
the binding being achieved at the bond indicated by a
Rio and Rn are each independently H, halo, Ci_6 alkoxy, substituted Ci_6 alkoxy, -NRaRb, or -OH; each Ra and Rb is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, -C(0)Ra, C6-10 aryl;
each Rc is independently H, phosphate, diphosphate, triphosphate, Ci_6 alkyl, or substituted Ci_6 alkyl;
each Rd is independently H, halo, Ci_6 alkyl, substituted Ci_6 alkyl, Ci_6 alkoxy, substituted Ci_6 alkoxy, -NH2, -NH(Ci_6 alkyl), -NH(substituted Ci_6 alkyl), - N(Ci_6 alkyl)2, -N(substituted Ci_6 alkyl)2, C6-io aryl, or heterocyclyl;
each Re is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, C6-io aryl, substituted C6-io aryl, heterocyclyl, or substituted heterocyclyl;
each Rf is independently H, Ci_6 alkyl, substituted Ci_6 alkyl, -C(0)Rd, phosphate, diphosphate, or triphosphate;
each n is independently 0, 1 , 2, or 3 ;
each p is independently 0, 1 , or 2; or
or (g) a pharmaceutically acceptable salt of any of (a) to (f), a tautomer of any of (a) to (f), or a pharmaceutically acceptable salt of the tautomer.
Loxoribine (7-allyl-8-oxoguanosine) (99).
Compounds disclosed in reference 100, including: Acylpiperazine compounds, Indoledione compounds, Tetrahydraisoquinoline (THIQ) compounds, Benzocyclodione compounds, Aminoazavinyl compounds, Aminobenzimidazole quinolinone (ABIQ) compounds (101 , 102), Hydrapthalamide compounds, Benzophenone compounds, Isoxazole compounds, Sterol compounds, Quinazilinone compounds, Pyrrole compounds (103), Anthraquinone compounds, Quinoxaline compounds, Triazine compounds, Pyrazalopyrimidine compounds, and Benzazole compounds (104).
Compounds disclosed in reference 105.
An aminoalkyl glucosaminide phosphate derivative, such as RC-529 (106, 107).
A phosphazene, such as poly[di(carboxylatophenoxy)phosphazene] ("PCPP") as described, for example, in references 108 and 109.
Small molecule immunopotentiators (SMIPs) such as:
N2-methyl-l -(2-methylpropyl)- lH-imidazo[4,5-c]quinoline-2,4-diamine
N2,N2-dimethyl- l-(2-methylpropyl)-lH-imidazo[4,5-c]quinoline-2,4-diamine
N2-ethyl-N2-methyl- 1 -(2-methylpropyl)- lH-imidazo[4,5-c]quinoline-2,4-diamine N2-methyl-l-(2-methylpropyl)-N2-propyl-lH-imidazo[4,5-c]quinoline-2,4- diamine
l-(2-methylpropyl)-N2-propyl-lH-imidazo[4,5-c]quinoline-2,4-diamine
N2-butyl-l-(2-methylpropyl)-lH-imidazo[4,5-c]quinoline-2,4-diamine
N2-butyl-N2-methyl-l-(2-methylpropyl)-lH-imidazo[4,5-c]quinoline-2,4-diamine
N2-methyl-l-(2-methylpropyl)-N2-pentyl-lH-imidazo[4,5-c]quinoline-2,4- diamine
N2-methyl-l-(2-methylpropyl)-N2-prop-2-enyl-lH-imidazo[4,5-c]quinoline-2,4- diamine
l-(2-methylpropyl)-2-[(phenylmethyl)thio]-lH-imidazo[4,5-c]quinolin-4-amine
1- (2-methylpropyl)-2-(propylthio)-lH-imidazo[4,5-c]quinolin-4-amine
2- [[4-amino-l-(2-methylpropyl)-lH-imidazo[4,5-c]quinolin-2- yl](methyl)amino]ethanol
2-[[4-amino-l-(2-methylpropyl)-lH-imidazo[4,5-c]quinolin-2- yl](methyl)amino]ethyl acetate
4-amino- 1 -(2-methylpropyl)- 1 ,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one
N2-butyl-l-(2-methylpropyl)-N4,N4-bis(phenylmethyl)-lH-imidazo[4,5-c]quinoline-
2,4-diamine
N2-butyl-N2-methyl-l-(2-methylpropyl)-N4,N4-bis(phenylmethyl)-lH- imidazo[4,5-c]quinoline-2,4-diamine
N2-methyl-l-(2-methylpropyl)-N4,N4-bis(phenylmethyl)-lH-imidazo[4,5- c]quinoline-2,4-diamine
N2,N2-dimethyl-l-(2-methylpropyl)-N4,N4-bis(phenylmethyl) H-imidazo[4,5- c]quinoline-2,4-diamine
1 - [4-amino-2- [methyl(propyl)amino] - 1 H-imidazo[4,5 -cjquinolin- 1 -yl] -2- methylpropan-2-ol
l-[4-amino-2-(propylamino)-lH-imidazo[4,5-c]quinolin-l-yl]-2-methylpropan-2- ol
N4,N4-dibenzyl-l-(2-methoxy-2-methylpropyl)-N2-propyl-lH-imidazo[4,5- c]quinoline-2,4-diamine.
[0177] The cytokine-inducing agents for use in the present invention may be modulators and/or agonists of Toll-Like Receptors (TLR). For example, they may be agonists of one or more of the human TLR1, TLR2, TLR3, TLR4, TLR7, TLR8, and/or TLR9 proteins. Preferred agents are agonists of TLR4 (e.g. , modified natural lipid As derived from enterobacterial lipopolysaccharides, phospholipid compounds, such as the synthetic phospholipid dimer, E6020), TLR7 (e.g., benzonaphthyridines, imidazoquinolines) and/or TLR9 (e.g., CpG oligonucleotides). These agents are useful for activating innate immunity pathways.
[0178] The cytokine-inducing agent can be added to the composition at various stages during its production. For example, it may be within an antigen composition, and this mixture can then be added to an oil-in- water emulsion. As an alternative, it may be within an oil-in-water emulsion, in which case the agent can either be added to the emulsion components before emulsification, or it can be added to the emulsion after emulsification. Similarly, the agent may be coacervated within the emulsion droplets. The location and distribution of the cytokine-inducing agent within the final composition will depend on its hydrophilic/lipophilic properties, e.g., the agent can be located in the aqueous phase, in the oil phase, and/or at the oil- water interface.
[0179] The cytokine-inducing agent can be conjugated to a separate agent, such as an antigen (e.g., CRM197). A general review of conjugation techniques for small molecules is provided in ref. 110. As an alternative, the adjuvants may be non-covalently associated with additional agents, such as by way of hydrophobic or ionic interactions.
[0180] Preferred cytokine-inducing agents are (a) benzonapthridine compounds; (b) immunostimulatory oligonucleotides and (c) 3dMPL.
[0181] Immunostimulatory oligonucleotides can include nucleotide
modifications/analogs such as phosphorothioate modifications and can be double-stranded or (except for RNA) single-stranded. References 111, 112, and 113disclose possible analog substitutions, e.g., replacement of guanosine with 2'-deoxy-7-deazaguanosine. The adjuvant effect of CpG oligonucleotides is further discussed in refs. 114 to 119. A CpG sequence may be directed to TLR9, such as the motif GTCGTT or TTCGTT (120). The CpG sequence may be specific for inducing a Thl immune response, such as a CpG- A ODN
(oligodeoxynucleotide), or it may be more specific for inducing a B cell response, such a CpG-B ODN. CpG-A and CpG-B ODNs are discussed in refs. 121-123. Preferably, the CpG is a CpG- A ODN. Preferably, the CpG oligonucleotide is constructed so that the 5' end is accessible for receptor recognition. Optionally, two CpG oligonucleotide sequences may be attached at their 3' ends to form "immunomers". See, for example, references 120 & 124- 126. A useful CpG adjuvant is CpG7909, also known as PROMUNE (TM) (Coley
Pharmaceutical Group, Inc.).
[0182] As an alternative, or in addition, to using CpG sequences, TpG sequences can be used (127). These oligonucleotides may be free from unmethylated CpG motifs.
[0183] The immunostimulatory oligonucleotide may be pyrimidine-rich. For example, it may comprise more than one consecutive thymidine nucleotide (e.g., TTTT, as disclosed in ref. 127), and/or it may have a nucleotide composition with >25 thymidine (e.g., >35 , >40 , >50 , >60 , >80 , etc.). For example, it may comprise more than one consecutive cytosine nucleotide (e.g., CCCC, as disclosed in ref. 127), and/or it may have a nucleotide composition with >25 cytosine (e.g., >35%, >40 , >50 , >60 , >80 , etc.). These oligonucleotides may be free from unmethylated CpG motifs.
[0184] Immunostimulatory oligonucleotides will typically comprise at least 20 nucleotides. They may comprise fewer than 100 nucleotides.
[0185] 3dMPL (also known as 3 de-O-acylated monophosphoryl lipid A or
3-0-desacyl-4'-monophosphoryl lipid A) is an adjuvant in which position 3 of the reducing end glucosamine in monophosphoryl lipid A has been de-acylated. 3dMPL has been prepared from a heptoseless mutant of Salmonella minnesota, and is chemically similar to lipid A but lacks an acid-labile phosphoryl group and a base-labile acyl group. It activates cells of the monocyte/macrophage lineage and stimulates release of several cytokines, including IL-1, IL-12, TNF-a and GM-CSF (see also ref. 128). Preparation of 3dMPL was originally described in reference 129.
[0186] 3dMPL can take the form of a mixture of related molecules, varying by their acylation (e.g., having 3, 4, 5 or 6 acyl chains, which may be of different lengths). The two glucosamine (also known as 2-deoxy-2-amino-glucose) monosaccharides are N-acylated at their 2-position carbons (i.e., at positions 2 and 2'), and there is also O-acylation at the 3' position. The group attached to carbon 2 has formula -NH-CO-CH2-CR1R1. The group attached to carbon 2' has formula -NH-CO-CH2-CR2R2'. The group attached to carbon 3' has formula -0-CO-CH2-CR3R3. A representative structure is:
[0187] Groups R1, R2 and R3 are each independently -(CH2)n-CH3. The value of n is preferably between 8 and 16, more preferably between 9 and 12, and is most preferably 10.
[0188] Groups R1 , R2' and R3' can each independently be: (a) -H; (b) -OH; or (c) - 0-CO-R4,where R4 is either -H or -(CH2)m-CH3, wherein the value of m is preferably between 8 and 16, and is more preferably 10, 12 or 14. At the 2 position, m is preferably 14. At the 2' position, m is preferably 10. At the 3' position, m is preferably 12. Groups R1 , R2 and R3 are thus preferably -O-acyl groups from dodecanoic acid, tetradecanoic acid or hexadecanoic acid.
[0189] When all of R1 , R2' and R3 are -H then the 3dMPL has only 3 acyl chains (one on each of positions 2, 2' and 3')· When only two of R1 , R2 and R3 are -H then the 3dMPL can have 4 acyl chains. When only one of R1 , R2' and R3' is -H then the 3dMPL can have 5 acyl chains. When none of R1 , R2' and R3' is -H then the 3dMPL can have 6 acyl chains. The 3dMPL adjuvant used according to the invention can be a mixture of these forms, with from 3 to 6 acyl chains, but it is preferred to include 3dMPL with 6 acyl chains in the mixture, and in particular to ensure that the hexaacyl chain form makes up at least 10% by weight of the total 3dMPL e.g., >20%, >30%, >40%, >50% or more. 3dMPL with 6 acyl chains has been found to be the most adjuvant-active form.
[0190] Thus the most preferred form of 3dMPL for inclusion in compositions of the invention has formula (IV), shown below.
[0191] Where 3dMPL is used in the form of a mixture then references to amounts or concentrations of 3dMPL in compositions of the invention refer to the combined 3dMPL species in the mixture.
[0192] In aqueous conditions, 3dMPL can form micellar aggregates or particles with different sizes e.g., with a diameter <150nm or >500nm. Either or both of these can be used with the invention, and the better particles can be selected by routine assay. Smaller particles {e.g., small enough to give a clear aqueous suspension of 3dMPL) are preferred for use according to the invention because of their superior activity (130). Preferred particles have a mean diameter less than 220nm, more preferably less than 200nm or less than 150nm or less than 120nm, and can even have a mean diameter less than lOOnm. In most cases, however, the mean diameter will not be lower than 50nm. These particles are small enough to be suitable for filter sterilization. Particle diameter can be assessed by the routine technique of dynamic light scattering, which reveals a mean particle diameter. Where a particle is said to have a diameter of x nm, there will generally be a distribution of particles about this mean, but at least 50% by number (e.g., >60%, >70%, >80%, >90%, or more) of the particles will have a diameter within the range x+25%.
[0193] 3dMPL can advantageously be used in combination with an oil-in-water emulsion. Substantially all of the 3dMPL may be located in the aqueous phase of the emulsion. [0194] The 3dMPL can be used on its own, or in combination with one or more further compounds. For example, it is known to use 3dMPL in combination with the QS21 saponin (131) (including in an oil-in- water emulsion (132)), with an immunostimulatory oligonucleotide, with both QS21 and an immunostimulatory oligonucleotide, with aluminum phosphate (133), with aluminum hydroxide (134), or with both aluminum phosphate and aluminum hydroxide.
Formula (IV)
Fatty adjuvants
[0195] Fatty adjuvants that can be used with the invention include the oil-in-water emulsions described above, and also include, for example:
• A phospholipid compound of formula I, II or III, or a salt thereof:
I II III
as defined in reference 135, such as 'ER 803058', 'ER 803732', 'ER 804053' , ER 804058', 'ER 804059', 'ER 804442', 'ER 804680', 'ER 804764' , ER 803022 or 'ER 804057' e.g. :
ER804057
ER-803022.
ER804057 is also called E6020. A phospholipid compound of formula I, II or III, or a salt thereof, can be used on its own, or in combination with one or more further compounds. For example, a compound of formula I, II or III, can be used in combination with an oil-in-water emulsion or a mineral-containing composition. In a particular embodiment, E6020 is used in combination with an oil-in- water emulsion (e.g. a squalene-water emulsion, such as MF59) or a mineral-containing composition (e.g., a mineral said such as an aluminum salt or a calcium salt).
• Derivatives of lipid A from Escherichia coli such as OM-174 (described in refs. 136 & 137).
• A formulation of a cationic lipid and a (usually neutral) co-lipid, such as
aminopropyl-dimethyl-myristoleyloxy-propanaminium bromide- diphytanoylphosphatidyl-ethanolamine ("VAXFECTIN (TM)") or aminopropyl- dimethyl-bis-dodecyloxy-propanaminium bromide-dioleoylphosphatidyl- ethanolamine ("GAP-DLRIE:DOPE"). Formulations containing (+)-N-(3- aminopropyl)-N,N-dimethyl-2,3-bis(syn-9-tetradeceneyloxy)-l-propanaminium salts are preferred (138).
• 3-O-deacylated monophosphoryl lipid A (see above).
• Compounds containing lipids linked to a phosphate-containing acyclic backbone, such as the TLR4 antagonist E5564 (139, 140):
• Lipopeptides (i.e., compounds comprising one or more fatty acid residues and two or more amino acid residues), such as lipopeptides based on glycerylcysteine. Specific examples of such peptides include compounds of the following formula in which each of R1 and R2 represents a saturated or unsaturated, aliphatic or mixed aliphatic - cycloaliphatic hydrocarbon radical having from 8 to 30, preferably 11 to 21, carbon atoms that is optionally also substituted by oxygen functions, R3 represents hydrogen or the radical R1-CO-O-CH2- in which R1 has the same meaning as above, and X represents an amino acid bonded by a peptide linkage and having a free, esterified or amidated carboxy group, or an amino acid sequence of from 2 to 10 amino acids of which the terminal carboxy group is in free, esterified or amidated form. In certain embodiments, the amino acid sequence comprises a D-amino acid, for example, D-glutamic acid (D-Glu) or D-gamma-carboxy- glutamic acid (D-Gla).
[0196] Bacterial lipopeptides generally recognize TLR2, without requiring TLR6 to participate. (TLRs operate cooperatively to provide specific recognition of various triggers, and TLR2 plus TLR6 together recognize peptidoglycans, while TLR2 recognizes lipopeptides without TLR6.) These are sometimes classified as natural lipopeptides and synthetic lipopeptides. Synthetic lipopeptides tend to behave similarly, and are primarily recognized by TLR2.
[0197] Lipopeptides suitable for use as adjuvants include compounds have the formula:
where the chiral center labeled * and the one labeled *** are both in the R configuration; the chiral center labeled ** is either in the R or S configuration;
each Rla and Rlb is independently an aliphatic or cycloaliphatic-aliphatic hydrocarbon group having 7-21 carbon atoms, optionally substituted by oxygen functions, or one of Rla and Rlb, but not both, is H;
R2 is an aliphatic or cycloaliphatic hydrocarbon group having 1-21 carbon atoms and
optionally substituted by oxygen functions;
n is 0 or 1 ;
As represents either -O-Kw-CO- or -NH-Kw-CO- , where Kw is an aliphatic
hydrocarbon group having 1-12 carbon atoms;
As1 is a D- or L-alpha-amino acid;
Z1 and Z2 each independently represent -OH or the N-terminal radical of a D- or L- alpha amino acid of an amino-(lower alkane)-sulfonic acid or of a peptide having up to 6 amino acids selected from the D- and L-alpha aminocarboxylic acids and amino-lower alkyl-sulfonic acids; and
Z3 is H or -CO-Z4, wher Z4 is -OH or the N-terminal radical of a D- or L-alpha amino acid of an amino-(lower alkane)- sulfonic acid or of a peptide having up to 6 amino acids selected from the D and L-alpha aminocarboxylic acids and amino-lower alkyl-sulfonic acids; or an ester or amide formed from the carboxylic acid of such compounds. Suitable amides include -N¾ and NH(lower alkyl), and suitable esters include C1-C4 alkyl esters, (lower alkyl or lower alkane, as used herein, refers to Ci-C6 straight chain or branched alkyls).
[0198] Such compounds are described in more detail in US 4,666,886. In one particular embodiment, the lipopeptide has the formula: [0199] Another example of a lipopeptide species is called LP40, and is an agonist of TLR2. Akdis, et al., Eur. J. Immunology, 33: 2717-26 (2003).
[0200] These are related to a known class of lipopeptides from E. coli, referred to as murein lipoproteins. Certain partial degradation products of those proteins called murein lipopetides are described in Hantke, et al., Eur. J. Biochem. , 34: 284-296 (1973). These comprise a peptide linked to N-acetyl muramic acid and are thus related to Muramyl peptides, which are described in Baschang, et al., Tetrahedron, 45(20): 6331-6360 (1989).
Aluminum salt adjuvants
[0201] The adjuvants known as "aluminum hydroxide" and "aluminum phosphate" may be used. These names are conventional, but are used for convenience only, as neither is a precise description of the actual chemical compound which is present (e.g., see chapter 9 of reference 74). The invention can use any of the "hydroxide" or "phosphate" adjuvants that are in general use as adjuvants.
[0202] The adjuvants known as "aluminum hydroxide" are typically aluminum oxyhydroxide salts, which are usually at least partially crystalline. Aluminum oxyhydroxide, which can be represented by the formula AIO(OH), can be distinguished from other aluminum compounds, such as aluminum hydroxide Al(OH)3, by infrared (IR) spectroscopy, in particular by the presence of an adsorption band at 1070cm 1 and a strong shoulder at 3090-3100cm 1 (chapter 9 of ref. 74). The de gree of crystallinity of an aluminum hydroxide adjuvant is reflected by the width of the diffraction band at half height (WHH), with poorly-crystalline particles showing greater line broadening due to smaller crystallite sizes. The surface area increases as WHH increases, and adjuvants with higher WHH values have been seen to have greater capacity for antigen adsorption. A fibrous morphology (e.g., as seen in transmission electron micrographs) is typical for aluminum hydroxide adjuvants. The pi of aluminum hydroxide adjuvants is typically about \ \, i.e., the adjuvant itself has a positive surface charge at physiological pH. Adsorptive capacities of between 1.8-2.6 mg protein per mg Al+++ at pH 7.4 have been reported for aluminum hydroxide adjuvants.
[0203] The adjuvants known as "aluminum phosphate" are typically aluminum hydroxyphosphates, often also containing a small amount of sulfate (i.e., aluminum hydroxyphosphate sulfate). They may be obtained by precipitation, and the reaction conditions and concentrations during precipitation influence the degree of substitution of phosphate for hydroxyl in the salt. Hydroxyphosphates generally have a PO4/AI molar ratio between 0.3 and 1.2. Hydroxyphosphates can be distinguished from strict A1P04 by the presence of hydroxyl groups. For example, an IR spectrum band at 3164cm"1 (e.g., when heated to 200°C) indicates the presence of structural hydroxyls (ch.9 of ref. 74)
[0204] The PO4/AI3"1" molar ratio of an aluminum phosphate adjuvant will generally be between 0.3 and 1.2, preferably between 0.8 and 1.2, and more preferably 0.95+0.1. The aluminum phosphate will generally be amorphous, particularly for hydroxyphosphate salts. A typical adjuvant is amorphous aluminum hydroxyphosphate with PO4/AI molar ratio between 0.84 and 0.92, included at 0.6mg Al3+/ml. The aluminum phosphate will generally be particulate (e.g., plate-like morphology as seen in transmission electron micrographs). Typical diameters of the particles are in the range 0.5-20μιη (e.g., about 5-10μιη) after any antigen adsorption. Adsorptive capacities of between 0.7-1.5 mg protein per mg Al+++ at pH 7.4 have been reported for aluminum phosphate adjuvants.
[0205] The point of zero charge (PZC) of aluminum phosphate is inversely related to the degree of substitution of phosphate for hydroxyl, and this degree of substitution can vary depending on reaction conditions and concentration of reactants used for preparing the salt by precipitation. PZC is also altered by changing the concentration of free phosphate ions in solution (more phosphate = more acidic PZC) or by adding a buffer such as a histidine buffer (makes PZC more basic). Aluminum phosphates used according to the invention will generally have a PZC of between 4.0 and 7.0, more preferably between 5.0 and 6.5, e.g., about 5.7.
[0206] Suspensions of aluminum salts used to prepare compositions of the invention may contain a buffer (e.g., a phosphate or a histidine or a Tris buffer), but this is not always necessary. The suspensions are preferably sterile and pyrogen-free. A suspension may include free aqueous phosphate ions e.g., present at a concentration between 1.0 and 20 mM, preferably between 5 and 15 mM, and more preferably about 10 mM. The suspensions may also comprise sodium chloride.
[0207] The invention can use a mixture of both an aluminum hydroxide and an aluminum phosphate. In this case there may be more aluminum phosphate than hydroxide e.g., a weight ratio of at least 2: 1 e.g., >5: 1, >6: 1, >7: 1 , >8: 1, >9: 1, etc.
[0208] The concentration of Al+++ in a composition for administration to a patient is preferably less than lOmg/ml e.g., <5 mg/ml, <4 mg/ml, <3 mg/ml, <2 mg/ml, <1 mg/ml, etc. A preferred range is between 0.3 and lmg/ml. A maximum of 0.85mg/dose is preferred.
[0209] As well as including one or more aluminum salt adjuvants, the adjuvant component may include one or more further adjuvant or immunostimulating agents. Such additional components include, but are not limited to: a benzonaphthyridine compound, a 3- O-deacylated monophosphoryl lipid A adjuvant ('3d-MPL'); and/or an oil-in-water emulsion. 3d-MPL has also been referred to as 3 de-O-acylated monophosphoryl lipid A or as
3-0-desacyl-4'-monophosphoryl lipid A. The name indicates that position 3 of the reducing end glucosamine in monophosphoryl lipid A is de-acylated. It has been prepared from a heptoseless mutant of S.minnesota, and is chemically similar to lipid A but lacks an acid- labile phosphoryl group and a base-labile acyl group. It activates cells of the
monocyte/macrophage lineage and stimulates release of several cytokines, including IL-1 , IL- 12, TNF-a and GM-CSF. Preparation of 3d-MPL was originally described in reference 129, and the product has been manufactured and sold by Corixa Corporation under the name MPL (TM). Further details can be found in refs 82 to 85.
[0210] The use of an aluminum hydroxide and/or aluminum phosphate adjuvant is useful, particularly in children, and antigens are generally adsorbed to these salts. Squalene- in- water emulsions are also preferred, particularly in the elderly. Useful adjuvant
combinations include combinations of Thl and Th2 adjuvants such as CpG and alum, or resiquimod and alum. A combination of aluminum phosphate and 3dMPL may be used. Other combinations that may be used include: alum and a benzonapthridine compound or a SMIP, a squalene-in-water emulsion (such as MF59) and a benzonapthridine compound or a SMIP, and E6020 and a squalene-in-water emulsion, such as MF59) or alum.
[0211] The compositions of the invention may elicit both a cell mediated immune response as well as a humoral immune response.
[0212] Two types of T cells, CD4 and CD8 cells, are generally thought necessary to initiate and/or enhance cell mediated immunity and humoral immunity. CD8 T cells can express a CD8 co-receptor and are commonly referred to as Cytotoxic T lymphocytes (CTLs). CD8 T cells are able to recognized or interact with antigens displayed on MHC Class I molecules.
[0213] CD4 T cells can express a CD4 co-receptor and are commonly referred to as T helper cells. CD4 T cells are able to recognize antigenic peptides bound to MHC class II molecules. Upon interaction with a MHC class II molecule, the CD4 cells can secrete factors such as cytokines. These secreted cytokines can activate B cells, cytotoxic T cells, macrophages, and other cells that participate in an immune response. Helper T cells or CD4+ cells can be further divided into two functionally distinct subsets: TH1 phenotype and TH2 phenotypes which differ in their cytokine and effector function. [0214] Activated TH1 cells enhance cellular immunity (including an increase in antigen-specific CTL production) and are therefore of particular value in responding to intracellular infections. Activated TH1 cells may secrete one or more of IL-2, IFN-γ, and TNF-β. A TH1 immune response may result in local inflammatory reactions by activating macrophages, NK (natural killer) cells, and CD8 cytotoxic T cells (CTLs). A TH1 immune response may also act to expand the immune response by stimulating growth of B and T cells with IL-12. TH1 stimulated B cells may secrete IgG2a.
[0215] Activated TH2 cells enhance antibody production and are therefore of value in responding to extracellular infections. Activated TH2 cells may secrete one or more of IL-4, IL-5, IL-6, and IL-10. A TH2 immune response may result in the production of IgGl , IgE, IgA and memory B cells for future protection.
[0216] An enhanced immune response may include one or more of an enhanced TH1 immune response and a TH2 immune response.
[0217] A TH1 immune response may include one or more of an increase in CTLs, an increase in one or more of the cytokines associated with a TH1 immune response (such as IL- 2, IFN-γ, and TNF-β), an increase in activated macrophages, an increase in NK activity, or an increase in the production of IgG2a. Preferably, the enhanced TH1 immune response will include an increase in IgG2a production.
[0218] A TH1 immune response may be elicited using a TH1 adjuvant. A TH1 adjuvant will generally elicit increased levels of IgG2a production relative to immunization of the antigen without adjuvant. TH1 adjuvants suitable for use in the invention may include for example saponin formulations, virosomes and virus like particles, non-toxic derivatives of enterobacterial lipopoly saccharide (LPS), immunostimulatory oligonucleotides.
Immunostimulatory oligonucleotides, such as oligonucleotides containing a CpG motif, are preferred TH1 adjuvants for use in the invention.
[0219] A TH2 immune response may include one or more of an increase in one or more of the cytokines associated with a TH2 immune response (such as IL-4, IL-5, IL-6 and IL-10), or an increase in the production of IgGl , IgE, IgA and memory B cells. Preferably, the enhanced TH2 immune response will include an increase in IgGl production.
[0220] A TH2 immune response may be elicited using a TH2 adjuvant. A TH2 adjuvant will generally elicit increased levels of IgGl production relative to immunization of the antigen without adjuvant. TH2 adjuvants suitable for use in the invention include, for example, mineral containing compositions, oil-emulsions, and ADP-ribosylating toxins and detoxified derivatives thereof. Mineral containing compositions, such as aluminium salts are preferred TH2 adjuvants for use in the invention.
[0221] A composition may include a combination of a THl adjuvant and a TH2 adjuvant. Preferably, such a composition elicits an enhanced THl and an enhanced TH2 response, i.e., an increase in the production of both IgGl and IgG2a production relative to immunization without an adjuvant. Still more preferably, the composition comprising a combination of a THl and a TH2 adjuvant elicits an increased THl and/or an increased TH2 immune response relative to immunization with a single adjuvant (i.e., relative to immunization with a THl adjuvant alone or immunization with a TH2 adjuvant alone).
[0222] The immune response may be one or both of a THl immune response and a TH2 response. Preferably, immune response provides for one or both of an enhanced THl response and an enhanced TH2 response.
[0223] The enhanced immune response may be one or both of a systemic and a mucosal immune response. Preferably, the immune response provides for one or both of an enhanced systemic and an enhanced mucosal immune response. Preferably the mucosal immune response is a TH2 immune response. Preferably, the mucosal immune response includes an increase in the production of IgA.
Methods of treatment, and administration
[0224] Compositions of the invention are suitable for administration to mammals, and the invention provides a method of inducing an immune response in a mammal, comprising the step of administering a composition (e.g., an immunogenic composition) of the invention to the mammal. The compositions (e.g., an immunogenic composition) can be used to produce a vaccine formulation for immunizing a mammal. The mammal is typically a human, and the RSV F protein is typically a human RSV F protein. However, the mammal can be any other mammal that is susceptible to infection with RSV, such as a cow that can be infected with bovine RSV. For example, the immune response may be raised following administration of a purified RSV F protein, an alphavirus particle, or self-replicating RNA.
[0225] The invention also provides the use of two or more pre-fusion chimerid proteins based on two or more different non-RSV (e.g., parainfluenza virus,
metapneumovirus) F pre-fusion proteins (i.e., PIV5 and NDV) that each have the same RSV F neutralizing epitopes mutated on the protein surface. Thus, inoculation with one chimeric pre-fusion F, and a second inoculation with the second pre-fusion F may prime several antibodies, some to RSV and some to the template protein backbone. The second inoculation may bias boosting of only the shared RSV F neutralizing epitopes.
[0226] The invention also provides a composition of the invention for use as a medicament, e.g., for use in immunizing a patient against RSV infection.
[0227] The invention also provides the use of a polypeptide as described above in the manufacture of a medicament for raising an immune response in a patient.
[0228] The immune response raised by these methods and uses will generally include an antibody response, preferably a protective antibody response. Methods for assessing antibody responses after RSV vaccination are well known in the art.
[0229] Compositions of the invention can be administered in a number of suitable ways, such as intramuscular injection (e.g., into the arm or leg), subcutaneous injection, intranasal administration, oral administration, intradermal administration, transcutaneous administration, transdermal administration, and the like. The appropriate route of administration will be dependent upon the age, health and other characteristics of the mammal. A clinician will be able to determine an appropriate route of administration based on these and other factors.
[0230] Immunogenic compositions, and vaccine formulations, may be used to treat both children and adults, including pregnant women. Thus a subject may be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old, or at least 55 years old. Preferred subjects for receiving the vaccines are the elderly (e.g., >50 years old, >60 years old, and preferably >65 years), the young (e.g., <6 years old, such as 4 - 6 years old, <5 years old), and pregnant women. The vaccines are not suitable solely for these groups, however, and may be used more generally in a population.
[0231] Treatment can be by a single dose schedule or a multiple dose schedule. Multiple doses may be used in a primary immunization schedule and/or in a booster immunization schedule. In a multiple dose schedule the various doses may be given by the same or different routes, e.g., a parenteral prime and mucosal boost, a mucosal prime and parenteral boost, etc. Administration of more than one dose (typically two doses) is particularly useful in immunologically naive patients. Multiple doses will typically be administered at least 1 week apart (e.g., about 2 weeks, about 3 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 16 weeks, and the like.).
[0232] Vaccine formulations produced using a composition of the invention may be administered to patients at substantially the same time as (e.g., during the same medical consultation or visit to a healthcare professional or vaccination centre) other vaccines. General
[0233] The term "comprising" encompasses "including" as well as "consisting" and "consisting essentially of" e.g., a composition "comprising" X may consist exclusively of X or may include something additional e.g., X + Y.
[0234] The word "substantially" does not exclude "completely" e.g., a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.
[0235] The term "about" in relation to a numerical value x means, for example, x+10 .
[0236] Unless specifically stated, a process comprising a step of mixing two or more components does not require any specific order of mixing. Thus components can be mixed in any order. Where there are three components then two components can be combined with each other, and then the combination may be combined with the third component, etc.
[0237] Where animal (and particularly bovine) materials are used in the culture of cells, they should be obtained from sources that are free from transmissible spongiform encaphalopathies (TSEs), and in particular free from bovine spongiform encephalopathy (BSE). Overall, it is preferred to culture cells in the total absence of animal-derived materials.
[0238] Where a compound is administered to the body as part of a composition then that compound may alternatively be replaced by a suitable prodrug.
[0239] Where a cell substrate is used for reassortment or reverse genetics procedures, it is preferably one that has been approved for use in human vaccine production e.g., as in Ph Eur general chapter 5.2.3.
[0240] Identity between polypeptide sequences is preferably determined by the Smith- Waterman homology search algorithm as implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with parameters gap open penalty=12 and gap extension penalty=l .
Table 2. Phospholipids
DDPC 1 ,2-Didecanoyl-sn-Glycero-3-phosphatidylcholine
DEPA 1 ,2-Dierucoyl-sn-Glycero-3-Phosphate
DEPC 1 ,2-Erucoyl-sn-Glycero-3-phosphatidylcholine DEPE l,2-Dierucoyl-sn-Glycero-3-phosphatidylethanolamine
DEPG l,2-Dierucoyl-sn-Glycero-3[Phosphatidyl-rac-(l -glycerol...)
DLOPC l,2-Linoleoyl-sn-Glycero-3-phosphatidylcholine
DLPA l,2-Dilauroyl-sn-Glycero-3-Phosphate
DLPC l,2-Dilauroyl-sn-Glycero-3-phosphatidylcholine
DLPE l,2-Dilauroyl-sn-Glycero-3-phosphatidylethanolamine
DLPG l,2-Dilauroyl-sn-Glycero-3[Phosphatidyl-rac-(l -glycerol...)
DLPS l,2-Dilauroyl-sn-Glycero-3-phosphatidylserine
DMG l,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine
DMPA l,2-Dimyristoyl-sn-Glycero-3-Phosphate
DMPC l,2-Dimyristoyl-sn-Glycero-3-phosphatidylcholine
DMPE l,2-Dimyristoyl-sn-Glycero-3-phosphatidylethanolamine
DMPG l,2-Myristoyl-sn-Glycero-3[Phosphatidyl-rac-(l -glycerol...)
DMPS l,2-Dimyristoyl-sn-Glycero-3-phosphatidylserine
DOPA l,2-Dioleoyl-sn-Glycero-3-Phosphate
DOPC l,2-Dioleoyl-sn-Glycero-3-phosphatidylcholine
DOPE l,2-Dioleoyl-sn-Glycero-3-phosphatidylethanolamine
DOPG l,2-Dioleoyl-sn-Glycero-3[Phosphatidyl-rac-(l-glycerol...)
DOPS l,2-Dioleoyl-sn-Glycero-3-phosphatidylserine
DPPA l,2-Dipalmitoyl-sn-Glycero-3-Phosphate
DPPC l,2-Dipalmitoyl-sn-Glycero-3-phosphatidylcholine
DPPE l,2-Dipalmitoyl-sn-Glycero-3-phosphatidylethanolamine
DPPG l,2-Dipalmitoyl-sn-Glycero-3[Phosphatidyl-rac-(l-glycerol...)
DPPS l,2-Dipalmitoyl-sn-Glycero-3-phosphatidylserine
DPyPE l,2-diphytanoyl-sn-glycero-3-phosphoethanolamine
DSPA l,2-Distearoyl-sn-Glycero-3-Phosphate
DSPC l,2-Distearoyl-sn-Glycero-3-phosphatidylcholine
DSPE l,2-Diostearpyl-sn-Glycero-3-phosphatidylethanolamine
DSPG l,2-Distearoyl-sn-Glycero-3[Phosphatidyl-rac-(l -glycerol...)
DSPS l,2-Distearoyl-sn-Glycero-3-phosphatidylserine
EPC Egg-PC
HEPC Hydrogenated Egg PC
HSPC High purity Hydrogenated Soy PC
HSPC Hydrogenated Soy PC
LYSOPC MYRISTIC l-Myristoyl-sn-Glycero-3-phosphatidylcholine LYSOPC PALMITIC l-Palmitoyl-sn-Glycero-3-phosphatidylcholine LYSOPC STEARIC l-Stearoyl-sn-Glycero-3-phosphatidylcholine Milk Sphingomyelin MPPC l-Myristoyl,2-palmitoyl-sn-Glycero 3 -phosphatidylcholine
MSPC l-Myristoyl,2-stearoyl-sn-Glycero-3-phosphatidylcholine
PMPC 1 -Palmitoyl,2-myristoyl-sn-Glycero-3-phosphatidylcholine
POPC 1 -Palmitoyl, 2-oleoyl- sn- Glycero- 3 -phosphatidylcholine
POPE l-Palmitoyl-2-oleoyl-sn-Glycero-3-phosphatidylethanolamine
POPG l,2-Dioleoyl-sn-Glycero-3[Phosphatidyl-rac-(l-glycerol)...]
PSPC 1 -Palmitoyl, 2- stearoyl- sn- Glycero- 3-phosphatidylcholine
SMPC l-Stearoyl,2-myristoyl-sn-Glycero-3-phosphatidylcholine
SOPC l-Stearoyl,2-oleoyl-sn-Glycero-3-phosphatidylcholine
SPPC l-Stearoyl,2-palmitoyl-sn-Glycero-3-phosphatidylcholine
EXEMPLIFICATION
1. Post-fusion structure and pre-fusion model
Post-Fusion RSV F Structure
[0241] A stable, non-aggregating soluble RSV F subunit antigen was prepared by deletion of the fusion peptide, transmembrane region, and cytoplasmic domain (FIG. 1). This engineered F was expressed efficiently and was readily purified. Electron microscopy of negatively stained specimens showed that it formed non-aggregated, homogeneous crutch- shaped molecules, consistent with post-fusion F trimers (FIG. 2A). This engineered F trimer was stable, and circular dichroism spectroscopy revealed no significant melting at temperatures up to 95°C (FIGS. 2B and 2C).
[0242] This RSV F protein was crystallized and its structure was determined by molecular replacement and three-fold non-crystallographic symmetry (NCS) averaging (Table 3 and FIG. 3). The structure does not include the p27 fragment (the peptide between the two furin sites that is lost upon cleavage), the fusion peptide, the transmembrane region, or the cytoplasmic domain (FIG. 4).
Table 3. Crystallographic data
Data collection statistics
Space Group P 2i 2i 2i Cell dimensions (A) a = 87.930
£ = 113.160 c = 311.370 α= β= γ= 90.00
Resolution limit (A) 50-3.2
Unique reflections 51,911
Unique reflections† 40 , 398
Redundancy 3.9 (3.7) ¥
Overall completeness ( ) 99.4 (99.4)
Overall completeness ( )† 77.0 (26.7)
Figure imgf000082_0001
Rsym ( ) 7.7 (71.0)
Refinement Statistics^
Polypeptide chains 3
Protein atoms 10,398
Residues in allowed regions of the Ramachandran plot ( ) 98.5
Residues in most favored regions of Ramachandran plot ( ) 83.5
RMSD bond lengths (A) 0.021
RMSD bond angles (deg) 2.053
Mean B values (A2) 15.71
Resolution range (A) 30-3.2
Figure imgf000082_0002
¥ Values in parentheses refer to data in the highest resolution shell
† Statistics for the data after anisotropic correction.
†† Refinement values for the data after anisotropic correction.
[0243] The overall architecture of post- fusion RSV F is shared with other post-fusion parainfluenza fusion proteins. The protein is composed of three tightly intertwined subunits, forming a globular head and an elongated stalk. Each subunit contains three domains, designated I, II, and III (FIGS. 4A-C). Domains I and II are at the top of the trimeric head and form a triangular crown. Domain III forms the base of the head. A long helix, HRA, extends from domain III and forms the trimeric coiled-coil in the center of the stalk. The HRB helix is tethered to domain II and reaches down to the head-distal end of the stalk, where it forms the outer coils of a six-helix bundle with the HRA interior coiled-coil. In full- length F, the hydrophobic fusion peptide (N-terminal to HRA) and the transmembrane region (C-terminal to HRB), would be juxtaposed at the bottom of the stalk and inserted into the target cell membrane.
[0244] Domains I and II of RSV, parainfluenza virus 3 (PIV3), and parainfluenza virus 5 (PIV5) F proteins are structurally conserved (FIGS. 5A and 5B). The only significant difference is in the orientation of the sole helix of domain I (η3 of RSV F and ot6 of PIV3 and PIV5 Fs) relative to their common β-sheets. In contrast, RSV F domain III has features that were not predicted from parainfluenza-based modeling (FIG. 6). When the four-stranded β-sheets of RSV F domain III and PIV3 F domain III are superimposed, key differences in the domains' helical regions are apparent. Helix HRA kinks at a more N-terminal position in RSV F than in PIV3 F, causing an approximately 60° difference in the rotation of the heads relative to the stalks (FIGS. 6A, 6B, 6D). Influenza hemagglutinins also vary in the orientations of their heads relative to their stalks, with 30°-50° differences in rotation between subtypes. (Ha, Y. et al., Embo Journal 21, 865-875 (2002)).
[0245] The RSV F domain III helical bundle region contains an extra helix (ot6), changing the orientation of the bundled helices relative to those in parainfluenza Fs (FIGS. 6A-C and FIG. 1). RSV F helices ot5 and ot6 are almost parallel and are exposed on the trimer surface; the equivalent to RSV F ot6 helix in the PIV3 helical bundle (ot5, FIG. 6C) is buried in the inter-subunit interface of the trimer. RSV F helices ot5 and ot6 form the epitope bound by the related neutralizing antibodies Palivizumab and Motavizumab. The structure of a complex between the Motavizumab Fab and a 24-residue RSV F peptide that includes ot5 and a6 has been reported (McLellan, J. S. et al. Nat Struct Mol Biol 17, 248-250 (2010)). Comparison between this structure and the post- fusion RSV F structure revealed a close match between the α5-α6 helices (r.m.s.d. = 0.52 A; FIG. 7A). Superposition of the two structures based on these helices models a complex between Motavizumab and post-fusion RSV F (FIG. 7B). This model reveals no steric hindrance that would prevent Motavizumab (or, presumably, Palivizumab) from binding to post- fusion RSV F. Binding of Palivizumab to the post-fusion F ectodomain in solution using surface plasmon resonance (KD of 4.2 x 10" 10 M) was confirmed.
[0246] Pre-fusion and post-fusion parainfluenza F structures reveal en bloc shifts of domains and large rearrangements of HRA and HRB. In domain III of the pre-fusion PIV5 F structure (the only reported pre-fusion parainfluenza F structure), HRA folds into three ot- helices and two β-strands rather than the long post- fusion HRA helix (Yin, H. S., et al.
Nature 439, 38-44 (2006)). However, when pre-fusion and post-fusion conformations of individual parainfluenza F protein domains are compared, the non-rearranging parts superimpose well. Superimposing post- fusion RSV F domains on their pre-fusion PIV5 F counterparts did not result in major clashes and positions all the pairs of cysteines that form interdomain disulfide bonds in proximity (FIG. 8B).
[0247] The resulting pre-fusion RSV F model reveals a feature not apparent from modeling pre-fusion RSV F domains based on the PIV5 pre-fusion domain structures (McLellan, J. S. et al. Nat Struct Mol Biol 17, 248-250 (2010)). The helices of the
Motavizumab epitope are exposed on the surface of the pre-fusion RSV F trimer, as they are on post-fusion RSV F trimer (FIG. 9). In the current pre-fusion RSV F model, the loop connecting β4 and HRC (part of domain III) would hinder access of Palivizumab or
Motavizumab to the epitope. However, the loop may have sufficient flexibility to adopt an alternative conformation that permits antibody binding (FIG. 9B).
[0248] The antigenic structure of RSV F has been mapped by a variety of techniques (FIG. 1). The best documented epitope clusters are designated A and C (Beeler, J. A. & van Wyke Coelingh, K. J Virol 63, 2941-2950 (1989)), and others have been proposed. The Motavizumab-peptide structure corroborated the location of site A, although it called into question the site's exposure on the RSF F trimer (McLellan, J. S. et al. Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol 17, 248-250 (2010)); a crystal structure of an RSV F peptide (residues 422-436) bound to the 101F neutralizing antibody corroborated the location of site C (McLellan, J. S. et al. J Virol 84, 12236-12244 (2010)). The post-fusion structure of RSV F and the pre-fusion RSV F model indicate that sites A and C remain exposed and structurally similar in both conformations (FIGS. 8A and 8B). Superposition of the lOlF-peptide complex on the RSV F pre-fusion model and post- fusion structure confirmed that 101 F would not clash with F in either conformation (FIG. 10).
[0249] Provided in the Appendix is the PDB file of the RSV F pre-fusion model based on the RSV F post-fusion structure and sequence/domain alignments to the PIV5 pre-fusion structure. The PDB file contains the atomic coordinates for the pre-fusion model, and can be used with suitable software for molecular visualization and analysis (e.g., Roger Sayle and E. James Milner- White. "RasMol: Biomolecular graphics for all", Trends in Biochemical Sciences (TIBS), September 1995, Vol. 20, No. 9, p. 374.) to display the model. Included in the model are the three subunit chains with the fusion peptide and HRA region folded as in PIV5, making significant contacts with DHL HRB regions of the three subunits trimerize into the pre-fusion stalk and are associated with Dl and DII.
2. Destablizing the post-fusion 6-helix bundle through deletion of the HRB helix [0250] An HRB deletion construct was designed to prevent formation of the post- fusion conformation. Two constructs have been designed to address this strategy. The first is a wild-type ectodomain lacking the HRB region (RSV F residues 1-483) call Del HRB:
[0251] The sequence presented below contain a signal peptide and a HIS tag
(GGSAGSGHHHHHH; SEQ ID NO:3). The pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
>RSV F delHRB HIS (SEQ ID NO: 28)
MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIE LSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMN YTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIEFQQKNNRLLE ITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSI IKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGS VSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSV ITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQE GKSLYVKGEPIINFYDPLVFPSGGSAGSGHHHHHH
[0252] The above sequence has both furin cleavage sites unaltered, and was expected to be processed by the cell. In addition, the above sequence has the wild-type fusion peptide sequence. In previous experiments, when the RSV F ectodomain-based proteins were cleaved by the cell and contained fusion peptides, they formed soluble aggregates with cellular debris in the form of RSV F rosettes. If this construct remained in the pre-fusion conformation (due to the lack of the HRB helix thought to be required for post-fusion conformation) than the fusion peptide should be burried in the RSV F head domain and should not form rosette aggreagates. This construct was expressed, purified by affinity purification and evaluated by EM analysis (FIG. 12).
[0253] It is clear both by its migration on an SEC column in the void volume, as well as from the EM micrograph that the construct formed rosettes similar to the rosettes formed by post-fusion RSV F proteins. This result was a surprise as it was hypothesized that the HRB is required to stabilize the HRA in its elongated helix formation (as it is observed that HRA peptides do not form trimers). Thus, we hypothesized that the fusion peptides, binding with one another or with cellular debris, are stabilizing the HRA helixes in their elongated, post-fusion formation.
[0254] We have hypothesized that the post- fusion like phenotype of the DelHRB construct was due to stabilization of the HRA into elongated helices by binding of the fusion peptides to one another or cellular debris. To test this hypothesis we are generating the following construct (DelHRB fusion peptide deletion: below) which is similar to the DelHRB but has the fusion peptide deletion consistent with our post-fusion trimer. We will test by EM microscopy the phenotype of the contract to see if it forms crutch-like structures similar to that of the post-fusion like phenotype observed in the DelHRB rosettes of if the construct forms pre-fusion head shapes, which are similar to the spherical shape of the lollipop phenotype published in the literature.
[0255] The sequence presented below contain a signal peptide and a HIS tag
(GGSAGSGHHHHHH; SEQ ID NO:3). The pre-fusion RSV F protein of the invention can contain the amino acid sequences shown below, with or without the signal peptide and/or HIS tag.
>RSV F delHRB fusion peptide deletion HIS (SEQ ID NO: 10)
MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYT
SVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRA
RRELPRFMN YTLNNAKKTN VTLS KKRKRRS AIAS G V A VS KVLHLEGE VNKIK
SALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIEF
QQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSN
NVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGS
NICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLC
NVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFS
NGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSGGS
AGS GHHHHHH
3. Prefusion Stabilization with Intrachain Disulfide Bond Formation
[0256] The RSV F model, based on the RSV F post- fusion structure and PIV5 pre- fusion structure, was used to engineer cysteine mutations intended to form disulfide bonds that stabilize RSV F in the pre-fusion conformation (Figure 11). The intrachain disulfide bond constructs were expressed, and were secreted from the cell into the media and then cleaved from F0 to F1/F2 to various degrees (Figure 14). RSV F T58C/V164C (expressed in mammalian cells) was found to express as a cleaved species which is secreted into the media. The material was purified by chelating purification and evaluated by the rosette/trimer HPLC-SEC assay using the Bio-Sil 250 SEC column with 2x PBS as mobile phase (Figure 15). As this is a cleaved F containing a fusion peptide, it was expected that would be in the postfusion form and would form rosettes and migrate in the void volume similar to postfusion RSV F rosettes (Figure 15A). If the cleaved F protein harboring a fusion peptide was folded in the prefusion form, one would expect the fusion peptide to be buried in the prefusion head region preventing rosette formation. Prefusion trimers should migrate in the included volume with a retention time similar to the RSV F postfusion trimer lacking the fusion peptide (Figure 15B). RSV F HRA Disulfide T58C V164C was run on HPLC-SEC, and the majority of material migrated in the column void volume, indicating the material was aggregating or forming rosettes of postfusion F. A smaller portion of the protein migrated in the included volume with a retention time consistent with an F trimer, suggesting some material formed the desired stabilized prefusion F.
[0257] The disulfide constructs were subsequently cloned into baculovirus expression vectors and three constructs (HRA disulfides N165C/V296C and K168C/V296C and HRB M396C/F483C) were expressed. K168C/V296C and M396C/F483C, which were cleaved when expressed in mammalian cells, were secreted by insect cells predominantly as an uncleaved species (as shown by anti-HIS western blot). Both constructs migrated in the void fraction, which was inconsistent with previous observations that uncleaved species run as monomers. The proteins may have aggregated by virtue of incorrect disulfide formation. Gel shift analysis using anti-HIS western (Figure 16) suggested that intra-chain disulfide bonds were not formed. The pure material taken from the void fraction of the SEC was analyzed with SDS-PAGE and coomassie staining, and each protein was found to be approximately 50% cleaved (Figure 16). A third disulfide construct was expressed and N165C/V296C was secreted predominantly as the desired cleaved product as judged by western blot (Figure 16A).
4. NDV F prefusion structure for further development of the RSV-NDV chimera subunit
A strategy for rescuing the RSV HRA prefusion epitopes was developed to generate an NDV F prefusion construct and mutate select residues of the HRA to those of RSV F. Initial attempts to replace the HRA of NDV with the HRA of RSV generated a construct which was not expressed/secreted from the cell. This indicated that the protein was misfolded. Further refinement of the residues of NDV F available for mutagenisis (i.e. those located on the protein surface) was required. A new construct, NDV F stabilized with a GCN trimerization domain (uncleaved) migrated as a trimer by SEC analysis. This was expected as this construct was shown to be a pre-fusion trimer by electron microscopy (Swanson et al, 2010).
5. EM analysis of RSV F with HRB and fusion peptide deletion related to NDV pre-fusion construct
[0258] The HRB -deleted RSV F harboring the fusion-peptide was generated, and the protein was purified. The construct migrated in the void volume of the SEC column consistent with RSV F rosettes. The construct was evaluated by EM and shown to form rosettes similar to the postfusion RSV F (Figure 18 A). An RSV F protein with both the HRB and fusion peptide deleted (Del-HRB Del-FP) was generated, expressed and purified. RSV F with the HRB and fusion peptide deleted ran partially as a trimer on SEC (Figure 18B). Gel analysis showed that RSV F del-HRB and Del-FP migrated both in the aggregation/rosette peak and trimer peak (Figure 18C). For comparison, the uncleaved NDV pre-fusion construct had very little material in the void fraction (Figure 18C). The RSV F Del-HRB Del-FP was collected from the trimer volume and evaluated by EM.
[0259] Electron micrographs of the NDV pre-fusion construct showed predominately the spherical heads expected for pre-fusion F (Figure 18D). A portion of the material seemed to be associated in rosette-like aggregates, which should not be permitted as the construct is uncleaved and pre-fusion. This amount of association may be due to aggregation by the HIS- tag, and may explain why the RSV Del-HRB Del-FP contained some aggregate/rosette even when the fusion peptide was not present. EM analysis of RSV F Del-HRB Del-FP showed that the material was heterogeneous (Figure 18E). RSV F Del-HRB Del-FP formed rosettelike structures similar to NDV F, as well as post-fusion like "crutches" and pre-fusion like "spheres".
R057 delHRB delFP trunc 6H (fusion peptide deleted)
MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRT
GWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQ
STPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRSAIASGVAV
SKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQ
LLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYML
TNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVV
QLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSV SFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMT SKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKG VDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSGGSAGSGHH HHHH** (SEQ ID NO: 10)
R105 delHRB delFP+linker trunk 6H (fusion peptide and linker deleted)
MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRT
GWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQ
STPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRSAIASGVAV
SKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQ
LLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYML
TNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVV
QLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSV
SFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMT
SKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKG
VDTVSVGNTLYYVNKQEGGGSAGSGHHHHHH** (SEQ ID NO:38)
6. Design of RSV F non-native HRB constructs
[0260] A stable RSV prefusion F was generated by replacing the HRB region with either the HRB region of NDV (with or without an additional glycine linker: HRB2) or PIV5. Mammalian expression of the non-native HRB constructs showed that each of the constructs were expressed and secreted well (Figure 19). Additionally, the band observed migrated consistent with the cleaved Fl species, suggesting that the proteins were properly processed. The constructs existed with or without fusion peptide (as indicated in Figure 19).
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The entire teachings of all documents cited herein are hereby incorporated herein by reference. APPENDIX
(APPENDIX discloses SEQ ID NOS 29-32, 29-32 and 29-32, respectively, in order of appearance)
HEADER — XX-XXX-9- xxxx
COMPND
SSBOND 1 CYS G 69 CYS G 212
SSBOND 2 CYS G 313 CYS G 343
SSBOND 3 CYS G 322 CYS G 333
SSBOND 4 CYS G 358 CYS G 367
SSBOND 5 CYS G 382 CYS G 393
SSBOND 6 CYS G 416 CYS G 422
LINKR CI NAGJ1535 ND2ASNG 70 NAG-ASN
LINKR CI NAGJ1545 ND2 ASN G 500 NAG-ASN
LINKR CI NAGJ1525 ND2ASNG 27 NAG-ASN
SSBOND 7 CYS H 69 CYSH 212
SSBOND 8 CYS H 313 CYSH 343
SSBOND 9 CYSH 322 CYSH 333
SSBOND 10 CYS H 358 CYS H 367
SSBOND 11 CYSH 382 CYSH 393
SSBOND 12 CYSH 416 CYSH 422
LINKR CI NAGK1535 ND2ASNH 70 NAG-ASN
LINKR OD1 ASN H 500 C7 NAGK1545 ASN-NAG
LINKR CI NAGK1545 ND2 ASN H 500 NAG-ASN
LINKR OD1 ASN H 27 07 NAGK1525 ASN-NAG1
LINKR CI NAGK1525 ND2ASNH 27 NAG-ASN
SSBOND 13 CYS I 69 CYS I 212
SSBOND 14 CYS I 313 CYS I 343
SSBOND 15 CYS I 322 CYS I 333
SSBOND 16 CYS I 358 CYS I 367
SSBOND 17 CYS I 382 CYS I 393
SSBOND 18 CYS I 416 CYS I 422
LINKR CI NAGL1535 ND2ASNI 70 NAG-ASN
LINKR CI NAGL1545 ND2 ASN I 500 NAG-ASN
LINKR CI NAGL1525 ND2ASNI 27 NAG-ASN
LINKR GLNG 98 PHE G 137 gap
LINKR ASN G 325 SER G 330 gap
LINKR LYS G 465 GLUG472 gap
LINKR NAGJ1535 NAG J1536 BETA 1-4
LINKR NAG J 1545 NAG J1546 BETA 1-4
LINKR NAG J1525 NAG J1526 BETA 1-4
LINKR PRO G 304 TYR G 306 gap
LINKR THRG 50 ILE G 309 gap
LINKR GLNH 98 PHE H 137 gap
LINKR ASN H 325 SER H 330 gap
LINKR LYS H 465 GLU H 472 gap
LINKR PRO H 304 TYR H 306 gap
LINKR THRH 50 ILE H 309 gap
LINKR GLN I 98 PHE 1137 gap
LINKR ASN I 325 SER I 330 gap
LINKR LYS 1465 GLU 1472 gap
LINKR PRO I 304 TYR I 306 gap
LINKR THRI 50 ILE I 309 gap
LINKR NAG Kl 535 NAG K1536 BETA 1-4
LINKR NAGL1535 NAGL1536 BETA 1-4
LINKR NAG Kl 545 NAG K1546 BETA 1-4
LINKR NAG LI 545 NAGL1546 BETA 1-4 LINKR NAG Kl 525 NAG K1526 BETA 1-4 LINKR NAG L1525 NAG LI 526 BETA 1-4
MODRES NAG J 1535 NAG-b-D RENAME MODRES NAG J 1536 NAG-b-D RENAME MODRES NAG J 1545 NAG-b-D RENAME MODRES NAG J 1546 NAG-b-D RENAME MODRES NAG J 1525 NAG-b-D RENAME MODRES NAG J 1526 NAG-b-D RENAME MODRES NAG K 1535 NAG-b-D RENAME MODRES NAG K 1536 NAG-b-D RENAME MODRES NAG K 1545 NAG-b-D RENAME MODRES NAG K 1546 NAG-b-D RENAME MODRES NAG K 1525 NAG-b-D RENAME MODRES NAG K 1526 NAG-b-D RENAME MODRES NAG L 1535 NAG-b-D RENAME MODRES NAG L 1536 NAG-b-D RENAME MODRES NAG L 1545 NAG-b-D RENAME MODRES NAG L 1546 NAG-b-D RENAME MODRES NAG L 1525 NAG-b-D RENAME MODRES NAG L 1526 NAG-b-D RENAME
CRYSTl 160.206 259.864 154.012 90.00 90.00 90.00 C 2 2 21 SCALE1 0.006242 0.000000 0.000000 0.00000
SCALE2 0.000000 0.003848 0.000000 0.00000
SCALE3 0.000000 0.000000 0.006493 0.00000
ATOM 1 N GLN G 26 24.299 30.940 -8.771 1.00 23.62 N
ATOM 2 CA GLN G 26 22.913 30.470 -9.055 1.00 23.82 C
ATOM 3 CB GLN G 26 22.260 29.923 -7.783 1.00 23.94 C
ATOM 4 CG GLN G 26 23.103 28.894 -7.043 1.00 28.83 C
ATOM 5 CD GLN G 26 24.309 29.508 -6.355 1.00 36.36 C
ATOM 6 OE1 GLN G 26 25.367 29.671 -6.963 1.00 39.09 O
ATOM 7 NE2 GLN G 26 24.176 29.785 -5.063 1.00 37.86 N
ATOM 8 C GLN G 26 22.064 31.593 -9.645 1.00 23.09 C
ATOM 9 O GLN G 26 22.368 32.772 -9.466 1.00 24.21 O
ATOM 10 N ASN G 27 21.079 31.214 -10.452 1.00 20.98 N
ATOM 11 CA ASN G 27 20.182 32.172 -11.089 1.00 19.70 C
ATOM 12 CB ASN G 27 20.879 32.850 -12.269 1.00 20.41 C
ATOM 13 CG ASN G 27 19.973 33.815 -13.014 1.00 23.56 C
ATOM 14 0D1 ASN G 27 19.456 34.775 -12.440 1.00 24.42 O
ATOM 15 ND2 ASN G 27 19.784 33.561 -14.310 1.00 27.70 N
ATOM 16 C ASN G 27 18.931 31.465 -11.578 1.00 18.42 C
ATOM 17 O ASN G 27 18.705 31.356 -12.783 1.00 18.47 O
ATOM 18 N ILE G 28 18.240 30.807 -10.655 1.00 16.54 N
ATOM 19 CA ILE G 28 17.060 30.044 -11.018 1.00 14.59 C
ATOM 20 CB ILE G 28 16.771 28.910 -10.025 1.00 14.01 C
ATOM 21 CGI ILE G 28 17.176 29.324 -8.610 1.00 15.60 C
ATOM 22 CD1 ILE G 28 16.159 30.199 -7.917 1.00 16.26 C
ATOM 23 CG2 ILE G 28 17.501 27.642 -10.441 1.00 12.57 C
ATOM 24 C ILE G 28 15.843 30.942 -11.157 1.00 13.86 C
ATOM 25 O ILE G 28 15.699 31.935 -10.443 1.00 13.70 O
ATOM 26 N THR G 29 15.098 30.702 -12.227 1.00 13.23 N
ATOM 27 CA THR G 29 13.968 31.532 -12.592 1.00 12.65 C
ATOM 28 CB THR G 29 14.306 32.435 -13.790 1.00 12.69 C
ATOM 29 0G1 THR G 29 15.728 32.530 -13.936 1.00 12.62 O
ATOM 30 CG2 THR G 29 13.723 33.825 -13.594 1.00 12.92 C
ATOM 31 C THR G 29 12.854 30.597 -13.010 1.00 12.47 C
ATOM 32 O THR G 29 13.106 29.526 -13.560 1.00 12.53 O
ATOM 33 N GLU G 30 11.622 31.050 -12.847 1.00 11.98 N
ATOM 34 CA GLU G 30 10.500 30.392 -13.480 1.00 11.68 C
ATOM 35 CB GLU G 30 9.587 29.781 -12.416 1.00 11.98 C
ATOM 36 CG GLU G 30 8.848 28.524 -12.856 1.00 13.38 C ATOM 37 CD GLUG 30 8.29527.732 -11.682 1.0016.03 C
ATOM 38 OE1 GLU G 30 7.55228.313 -10.863 1.0016.65 O
ATOM 39 OE2GLUG 30 8.57726.519 -11.596 1.0017.06 O
ATOM 40 C GLUG 30 9.743 31.433 -14.281 1.0011.39 C
ATOM 41 O GLUG 30 9.521 32.547 -13.806 1.0011.50 O
ATOM 42 N GLUG 31 9.449 31.119 -15.535 1.0011.11 N
ATOM 43 CA GLUG 31 8.573 31.975 -16.305 1.0011.06 C
ATOM 44 CB GLUG 31 9.345 32.716 -17.394 1.0011.48 C
ATOM 45 CG GLUG 31 9.02632.268 -18.803 1.0013.90 C
ATOM 46 CD GLUG 31 9.62233.190 -19.843 1.0017.27 C
ATOM 47 OE1 GLU G 31 8.85233.749 -20.653 1.0017.55 O
ATOM 48 OE2GLUG 31 10.849 33.418 -19.804 1.0018.73 O
ATOM 49 C GLUG 31 7.37031.240 -16.871 1.0010.47 C
ATOM 50 O GLUG 31 7.459 30.080-17.274 1.0010.12 O
ATOM 51 N PHEG 32 6.22031.890 -16.753 1.0010.15 N
ATOM 52 CA PHEG 32 4.93231.235 -16.887 1.009.62 C
ATOM 53 CB PHEG 32 3.967 31.777 -15.832 1.009.42 C
ATOM 54 CG PHEG 32 2.52431.512-16.141 1.009.27 C
ATOM 55 CD1 PHE G 32 2.021 30.222 -16.085 1.009.37 C
ATOM 56 CE1 PHE G 32 0.701 29.960-16.407 1.009.52 C
ATOM 57 CZ PHEG 32 -0.132 30.993 -16.800 1.009.82 C
ATOM 58 CE2PHEG 32 0.36232.285 -16.877 1.0010.13 C
ATOM 59 CD2PHEG 32 1.681 32.541 -16.536 1.0010.06 C
ATOM 60 C PHEG 32 4.38631.524 -18.276 1.009.64 C
ATOM 61 O PHEG 32 4.479 32.650 -18.763 1.009.84 O
ATOM 62 N TY G 33 3.84630.501 -18.926 1.009.59 N
ATOM 63 CA TY G 33 3.34230.662 -20.281 1.009.67 C
ATOM 64 CB TY G 33 3.951 29.617 -21.212 1.009.52 C
ATOM 65 CG TYRG 33 5.42229.834-21.467 1.0010.94 C
ATOM 66 CD1 TYRG 33 6.37929.220 -20.670 1.0012.23 C
ATOM 67 CE1 TYRG 33 7.72629.448 -20.870 1.0012.93 C
ATOM 68 CZ TYRG 33 8.128 30.348 -21.833 1.0013.47 C
ATOM 69 OH TYRG 33 9.469 30.588 -22.028 1.0014.54 O
ATOM 70 CE2TYRG 33 7.195 31.019 -22.594 1.0013.56 C
ATOM 71 CD2TYRG 33 5.85030.781 -22.388 1.0012.96 C
ATOM 72 C TYRG 33 1.82430.604-20.327 1.009.94 C
ATOM 73 O TYRG 33 1.23429.530-20.446 1.0010.16 O
ATOM 74 N GLNG 34 1.199 31.769 -20.211 1.0010.06 N
ATOM 75 CA GLNG 34 -0.225 31.846 -19.927 1.0010.01 C
ATOM 76 CB GLNG 34 -0.649 33.302 -19.751 1.0010.22 C
ATOM 77 CG GLNG 34 -2.138 33.486 -19.551 1.0011.12 C
ATOM 78 CD GLNG 34 -2.485 34.867 -19.039 1.0013.13 C
ATOM 79 OE1 GLN G 34 -2.668 35.804 -19.819 1.0014.24 O
ATOM 80 NE2GLNG 34 -2.553 35.007 -17.719 1.0013.79 N
ATOM 81 C GLNG 34 -1.039 31.198 -21.039 1.009.94 C
ATOM 82 O GLNG 34 -2.165 30.752 -20.819 1.0010.08 O
ATOM 83 N SERG 35 -0.468 31.167 -22.238 1.009.87 N
ATOM 84 CA SERG 35 -1.185 30.690 -23.415 1.009.91 C
ATOM 85 CB SERG 35 -0.619 31.337 -24.684 1.0010.03 C
ATOM 86 OG SERG 35 0.77631.572 -24.564 1.0010.81 O
ATOM 87 C SERG 35 -1.11929.167 -23.518 1.009.56 C
ATOM 88 O SERG 35 -1.68828.566 -24.431 1.009.59 O
ATOM 89 N THRG 36 -0.41728.553 -22.572 1.009.21 N
ATOM 90 CA THRG 36 -0.209 27.113 -22.573 1.009.06 C
ATOM 91 CB THRG 36 1.23026.755 -23.010 1.009.49 C
ATOM 92 OG1 THR G 36 1.49327.310 -24.305 1.0010.82 O
ATOM 93 CG2THRG 36 1.41025.245 -23.074 1.009.45 C
ATOM 94 C THRG 36 -0.45526.599 -21.162 1.008.77 C
ATOM 95 O THRG 36 -0.171 25.445 -20.845 1.008.60 O
ATOM 96 N CYS G 37 -0.98227.478 -20.315 1.008.69 N ATOM 97 CA CYSG 37 -1.09727.201 -18.890 1.008.69 C
ATOM 98 CB CYSG 37 -2.468 26.605 -18.571 1.008.81 C
ATOM 99 SG CYSG 37 -3.00326.848 -16.864 1.0010.80 S
ATOM 100 C CYS G 37 0.00526.263 -18.414 1.008.27 C
ATOM 101 O CYSG 37 -0.268 25.166 -17.926 1.008.27 O
ATOM 102 N SE G 38 1.251 26.687 -18.586 1.007.92 N
ATOM 103 CA SERG 38 2.38625.886 -18.157 1.007.51 C
ATOM 104 CB SERG 38 2.81724.924 -19.264 1.007.63 C
ATOM 105 OG SERG 38 3.39225.627 -20.351 1.008.54 O
ATOM 106 C SERG 38 3.55826.757 -17.735 1.007.02 C
ATOM 107 O SERG 38 3.66327.917 -18.132 1.006.83 O
ATOM 108 N ALAG 39 4.40726.198 -16.882 1.006.64 N
ATOM 109 CA ALAG 39 5.46626.961 -16.245 1.006.58 C
ATOM 110 CB ALAG 39 5.13627.195 -14.782 1.006.67 C
ATOM 111 C ALAG 39 6.78926.222 -16.382 1.006.93 C
ATOM 112 O ALAG 39 6.84224.998 -16.261 1.007.38 O
ATOM 113 N VALG 40 7.84326.966 -16.698 1.006.87 N
ATOM 114 CA VALG 40 9.17526.388 -16.797 1.006.55 C
ATOM 115 CB VALG 40 9.741 26.507 -18.222 1.006.22 C
ATOM 116 CGI VALG 40 11.23726.233 -18.223 1.006.52 C
ATOM 117 CG2VALG 40 9.01825.553 -19.160 1.00 6.62 C
ATOM 118 C VALG 40 10.14027.033 -15.813 1.00 6.73 C
ATOM 119 O VALG 40 10.30228.253 -15.789 1.006.83 O
ATOM 120 N SERG 41 10.77226.198 -14.997 1.006.86 N
ATOM 121 CA SERG 41 11.897 26.625 -14.181 1.006.75 C
ATOM 122 CB SERG 41 11.97425.785 -12.905 1.007.06 C
ATOM 123 OG SERG 41 10.751 25.110-12.666 1.007.50 O
ATOM 124 C SERG 41 13.20626.525 -14.958 1.006.56 C
ATOM 125 O SERG 41 13.52625.482 -15.529 1.006.08 O
ATOM 126 N LYSG 42 13.97227.612-14.946 1.007.02 N
ATOM 127 CA LYS G 42 15.14027.757 -15.809 1.007.83 C
ATOM 128 CB LYS G 42 14.949 28.933 -16.769 1.008.15 C
ATOM 129 CG LYS G 42 13.66628.888 -17.578 1.009.75 C
ATOM 130 CD LYS G 42 13.51030.148 -18.414 1.0012.62 C
ATOM 131 CE LYS G 42 12.36030.022-19.398 1.0014.04 C
ATOM 132 NZ LYS G 42 12.643 30.734 -20.675 1.0014.96 N
ATOM 133 C LYS G 42 16.39427.988 -14.971 1.007.80 C
ATOM 134 O LYS G 42 16.32328.557 -13.882 1.008.15 O
ATOM 135 N GLYG 43 17.55027.717 -15.566 1.007.59 N
ATOM 136 CA GLYG 43 18.82028.160 -15.002 1.007.35 C
ATOM 137 C GLYG 43 19.529 27.058 -14.240 1.007.10 C
ATOM 138 O GLYG 43 20.29427.323 -13.313 1.007.13 O
ATOM 139 N TYRG 44 19.309 25.819 -14.668 1.007.01 N
ATOM 140 CA TYRG 44 19.92224.656-14.033 1.006.89 C
ATOM 141 CB TYRG 44 18.878 23.561 -13.815 1.00 6.88 C
ATOM 142 CG TYRG 44 17.80923.928 -12.816 1.006.41 C
ATOM 143 CD1TYRG 44 16.553 24.343 -13.236 1.006.62 C
ATOM 144 CE1TYRG 44 15.58024.703 -12.325 1.006.48 C
ATOM 145 CZ TYRG 44 15.86224.662 -10.976 1.006.88 C
ATOM 146 OH TYRG 44 14.89725.025 -10.065 1.007.50 O
ATOM 147 CE2TYRG 44 17.11024.279 -10.536 1.006.68 C
ATOM 148 CD2TYRG 44 18.077 23.922-11.454 1.005.91 C
ATOM 149 C TYRG 44 21.06024.106-14.886 1.006.86 C
ATOM 150 O TYRG 44 21.01224.190-16.113 1.007.14 O
ATOM 151 N LEU G 45 21.97923.385 -14.249 1.006.44 N
ATOM 152 CA LEU G 45 23.14622.842-14.946 1.00 6.12 C
ATOM 153 CB LEU G 45 24.42523.552-14.482 1.006.31 C
ATOM 154 CG LEU G 45 24.53425.052-14.775 1.00 6.38 C
ATOM 155 CD1LEUG 45 25.62425.690 -13.928 1.007.05 C
ATOM 156 CD2LEUG 45 24.78725.299 -16.255 1.007.05 C ATOM 157 C LEU G 45 23.27921.312-14.800 1.005.84 C
ATOM 158 O LEU G 45 23.33320.797 -13.683 1.005.94 O
ATOM 159 N SE G 46 23.47020.620-15.929 1.005.43 N
ATOM 160 CA SERG 46 23.249 19.157 -16.047 1.005.26 C
ATOM 161 CB SERG 46 22.913 18.795 -17.498 1.005.21 C
ATOM 162 OG SERG 46 24.090 18.532-18.243 1.004.95 O
ATOM 163 C SERG 46 24.481 18.355 -15.585 1.005.51 C
ATOM 164 O SERG 46 25.480 18.961 -15.200 1.006.03 O
ATOM 165 N ALAG 47 24.453 17.015 -15.656 1.005.24 N
ATOM 166 CA ALAG 47 25.584 16.224-15.104 1.004.83 C
ATOM 167 CB ALAG 47 25.690 16.412-13.599 1.005.01 C
ATOM 168 C ALAG 47 25.854 14.751 -15.494 1.004.35 C
ATOM 169 O ALAG 47 24.926 13.972 -15.719 1.004.45 O
ATOM 170 N LEU G 48 27.119 14.348 -15.323 1.003.67 N
ATOM 171 CA LEU G 48 27.564 12.948 -15.451 1.00 3.15 C
ATOM 172 CB LEU G 48 28.365 12.755 -16.750 1.002.78 C
ATOM 173 CG LEU G 48 27.659 12.681 -18.108 1.002.18 C
ATOM 174 CD1LEUG 48 28.223 11.532 -18.935 1.002.00 C
ATOM 175 CD2LEUG 48 26.156 12.531 -17.934 1.003.94 C
ATOM 176 C LEU G 48 28.443 12.517 -14.259 1.003.06 C
ATOM 177 O LEU G 48 29.670 12.486 -14.373 1.003.27 O
ATOM 178 N ARGG 49 27.810 12.061 -13.177 1.002.91 N
ATOM 179 CA ARGG 49 28.509 11.788 -11.915 1.002.88 C
ATOM 180 CB ARGG 49 27.538 11.277 -10.847 1.002.69 C
ATOM 181 CG ARGG 49 28.117 11.273 -9.440 1.002.15 C
ATOM 182 CD ARGG 49 28.015 9.897 -8.806 1.002.00 C
ATOM 183 NE ARGG 49 29.322 9.271 -8.623 1.005.18 N
ATOM 184 CZ ARGG 49 29.526 7.956 -8.629 1.007.68 C
ATOM 185 NH1 ARGG 49 28.518 7.129 -8.866 1.00 8.32 N
ATOM 186 NH2ARGG 49 30.748 7.469 -8.455 1.00 8.12 N
ATOM 187 C ARGG 49 29.678 10.816 -12.065 1.003.09 C
ATOM 188 O ARGG 49 29.570 9.796 -12.747 1.003.08 O
ATOM 189 N THRG 50 30.820 11.189 -11.489 1.00 3.37 N
ATOM 190 CA THRG 50 32.099 10.564 -11.823 1.003.55 C
ATOM 191 CB THRG 50 32.487 10.773 -13.299 1.00 3.25 C
ATOM 192 OG1THRG 50 32.842 12.144-13.519 1.002.66 O
ATOM 193 CG2THRG 50 31.328 10.401 -14.212 1.003.46 C
ATOM 194 C THRG 50 33.259 10.968 -10.908 1.004.07 C
ATOM 195 O THRG 50 33.768 10.130 -10.165 1.004.35 O
ATOM 196 N GLYG 51 33.818 12.158 -11.108 1.004.24 N
ATOM 197 CA GLYG 51 34.942 12.544-10.272 1.004.78 C
ATOM 198 C GLYG 51 34.692 11.849 -8.951 1.004.98 C
ATOM 199 O GLYG 51 33.618 12.018 -8.375 1.005.00 O
ATOM 200 N TRPG 52 35.476 10.816 -8.667 1.005.34 N
ATOM 201 CA TRPG 52 35.123 9.926 -7.569 1.005.42 C
ATOM 202 CB TRPG 52 34.864 8.497 -8.049 1.005.75 C
ATOM 203 CG TRPG 52 33.714 8.373 -9.001 1.006.38 C
ATOM 204 CD1 TRPG 52 33.776 7.964 -10.300 1.007.27 C
ATOM 205 NE1 TRPG 52 32.533 8.031 -10.878 1.007.46 N
ATOM 206 CE2TRPG 52 31.627 8.449 -9.938 1.007.15 C
ATOM 207 CD2TRPG 52 32.331 8.658 -8.735 1.007.02 C
ATOM 208 CE3TRPG 52 31.627 9.102 -7.608 1.006.83 C
ATOM 209 CZ3TRPG 52 30.261 9.289 -7.711 1.006.73 C
ATOM 210 CH2TRPG 52 29.589 9.062 -8.922 1.007.13 C
ATOM 211 CZ2 TRPG 52 30.252 8.637 -10.041 1.00 6.82 C
ATOM 212 C TRPG 52 36.148 9.926 -6.456 1.005.34 C
ATOM 213 O TRPG 52 37.349 10.027 -6.698 1.005.47 O
ATOM 214 N TYRG 53 35.670 9.629 -5.256 1.005.29 N
ATOM 215 CA TYRG 53 36.528 9.560 -4.093 1.005.58 C
ATOM 216 CB TYRG 53 36.260 10.754 -3.176 1.005.51 C ATOM 217 CG TY G 53 37.079 10.756 -1.910 1.00 6.59 C
ATOM 218 CD1 TY G 53 38.312 11.391 -1.858 1.00 8.25 c
ATOM 219 CE1 TY G 53 39.043 11.436 -0.685 1.00 9.40 c
ATOM 220 CZ TYR G 53 38.524 10.875 0.462 1.00 9.24 c
ATOM 221 OH TYR G 53 39.246 10.915 1.633 1.00 9.61 o
ATOM 222 CE2 TYR G 53 37.287 10.272 0.443 1.00 8.78 c
ATOM 223 CD2 TYR G 53 36.559 10.247 -0.730 1.00 7.93 c
ATOM 224 C TYR G 53 36.286 8.245 -3.364 1.00 5.74 c
ATOM 225 O TYR G 53 35.186 7.996 -2.870 1.00 6.19 o
ATOM 226 N THR G 54 37.221 7.317 -3.532 1.00 6.04 N
ATOM 227 CA THR G 54 37.132 6.013 -2.888 1.00 6.67 c
ATOM 228 CB THR G 54 38.232 5.060 -3.396 1.00 6.97 c
ATOM 229 OG1 THR G 54 37.876 4.562 -4.691 1.00 7.51 o
ATOM 230 CG2 THR G 54 38.409 3.889 -2.442 1.00 7.98 c
ATOM 231 C THR G 54 37.254 6.158 -1.376 1.00 6.97 c
ATOM 232 O THR G 54 37.900 7.083 -0.884 1.00 7.32 o
ATOM 233 N SER G 55 36.616 5.254 -0.639 1.00 7.24 N
ATOM 234 CA SER G 55 37.025 4.966 0.732 1.00 7.65 c
ATOM 235 CB SER G 55 36.459 6.009 1.705 1.00 7.69 c
ATOM 236 OG SER G 55 36.690 5.632 3.053 1.00 7.51 o
ATOM 237 C SER G 55 36.629 3.561 1.171 1.00 8.03 c
ATOM 238 O SER G 55 35.510 3.109 0.924 1.00 8.43 o
ATOM 239 N VAL G 56 37.522 2.919 1.915 1.00 8.14 N
ATOM 240 CA VAL G 56 37.401 1.500 2.215 1.00 8.41 c
ATOM 241 CB VAL G 56 38.732 0.763 1.967 1.00 8.72 c
ATOM 242 CGI VAL G 56 38.479 -0.703 1.654 1.00 9.29 c
ATOM 243 CG2 VAL G 56 39.509 1.433 0.843 1.00 9.51 c
ATOM 244 C VAL G 56 37.005 1.312 3.673 1.00 8.19 c
ATOM 245 O VAL G 56 37.760 1.658 4.578 1.00 8.54 o
ATOM 246 N ILE G 57 35.784 0.845 3.898 1.00 7.91 N
ATOM 247 CA ILE G 57 35.255 0.779 5.249 1.00 7.64 c
ATOM 248 CB ILE G 57 33.912 1.510 5.372 1.00 7.35 c
ATOM 249 CGI ILE G 57 34.063 2.964 4.918 1.00 7.25 c
ATOM 250 CD1 ILE G 57 32.922 3.860 5.343 1.00 8.42 c
ATOM 251 CG2 ILE G 57 33.404 1.449 6.804 1.00 7.52 c
ATOM 252 C ILE G 57 35.125 -0.655 5.739 1.00 7.69 c
ATOM 253 O ILE G 57 34.629 -1.527 5.025 1.00 7.79 o
ATOM 254 N THR G 58 35.726 -0.917 6.894 1.00 7.85 N
ATOM 255 CA THR G 58 35.912 -2.275 7.379 1.00 8.15 c
ATOM 256 CB THR G 58 37.405 -2.631 7.469 1.00 8.14 c
ATOM 257 OG1 THR G 58 38.159 -1.761 6.615 1.00 8.62 o
ATOM 258 CG2 THR G 58 37.634 -4.075 7.053 1.00 7.94 c
ATOM 259 C THR G 58 35.291 -2.414 8.763 1.00 8.20 c
ATOM 260 O THR G 58 35.589 -1.633 9.664 1.00 8.18 o
ATOM 261 N ILE G 59 34.396 -3.384 8.915 1.00 8.54 N
ATOM 262 CA ILE G 59 33.617 -3.525 10.143 1.00 9.23 c
ATOM 263 CB ILE G 59 32.144 -3.139 9.912 1.00 8.92 c
ATOM 264 CGI ILE G 59 32.031 -1.688 9.443 1.00 9.27 c
ATOM 265 CD1 ILE G 59 30.626 -1.285 9.045 1.00 10.89 c
ATOM 266 CG2 ILE G 59 31.326 -3.377 11.170 1.00 8.74 c
ATOM 267 C ILE G 59 33.648 -4.973 10.621 1.00 10.02 c
ATOM 268 O ILE G 59 33.170 -5.865 9.921 1.00 10.20 o
ATOM 269 N GLU G 60 34.251 -5.221 11.779 1.00 10.95 N
ATOM 270 CA GLU G 60 34.630 -6.586 12.133 1.00 12.13 c
ATOM 271 CB GLU G 60 35.311 -6.605 13.510 1.00 12.44 c
ATOM 272 CG GLU G 60 36.583 -5.750 13.558 1.00 15.04 c
ATOM 273 CD GLU G 60 37.500 -6.089 14.724 1.00 19.34 c
ATOM 274 OE1 GLU G 60 37.163 -5.716 15.869 1.00 20.63 o
ATOM 275 OE2 GLU G 60 38.625 -6.578 14.476 1.00 21.19 o
ATOM 276 C GLU G 60 33.397 -7.503 12.086 1.00 12.46 c ATOM 277 O GLU G 60 32.369 -7.164 12.677 1.00 12.68
ATOM 278 N LEU G 61 33.448 -8.627 11.361 1.00 12.80
ATOM 279 CA LEU G 61 32.635 -9.731 11.843 1.00 12.71
ATOM 280 CB LEU G 61 32.816 -11.079 11.148 1.00 12.55
ATOM 281 CG LEU G 61 31.902 -12.059 11.912 1.00 12.39
ATOM 282 CD1 LEU G 61 30.438 -11.897 11.514 1.00 13.14
ATOM 283 CD2 LEU G 61 32.335 -13.513 11.814 1.00 12.50
ATOM 284 C LEU G 61 33.223 -9.800 13.207 1.00 12.94
ATOM 285 O LEU G 61 34.388 -10.187 13.351 1.00 12.78
ATOM 286 N SE G 62 32.676 -8.895 13.997 1.00 13.61
ATOM 287 CA SE G 62 32.941 -8.871 15.409 1.00 14.70
ATOM 288 CB SER G 62 32.339 -7.611 16.023 1.00 14.52
ATOM 289 OG SER G 62 32.798 -6.455 15.345 1.00 14.80
ATOM 290 C SER G 62 32.342 -10.111 16.051 1.00 15.48
ATOM 291 O SER G 62 31.132 -10.187 16.263 1.00 15.50
ATOM 292 N ASN G 63 33.164 -11.141 16.199 1.00 16.61
ATOM 293 CA ASN G 63 32.650 -12.422 16.635 1.00 17.77
ATOM 294 CB ASN G 63 33.597 -13.559 16.266 1.00 17.73
ATOM 295 CG ASN G 63 32.857 -14.834 15.934 1.00 18.52
ATOM 296 OD1 ASN G 63 31.848 -15.156 16.561 1.00 18.29
ATOM 297 ND2 ASN G 63 33.295 -15.516 14.883 1.00 19.40
ATOM 298 C ASN G 63 32.325 -12.448 18.119 1.00 18.53
ATOM 299 O ASN G 63 32.967 -11.768 18.919 1.00 18.82
ATOM 300 N ILE G 64 31.240 -13.135 18.457 1.00 19.60
ATOM 301 CA ILE G 64 30.912 -13.413 19.848 1.00 21.04
ATOM 302 CB ILE G 64 29.403 -13.648 20.038 1.00 20.60
ATOM 303 CGI ILE G 64 28.593 -12.612 19.259 1.00 20.13
ATOM 304 CD1 ILE G 64 27.150 -12.497 19.722 1.00 20.19
ATOM 305 CG2 ILE G 64 29.040 -13.615 21.514 1.00 20.74
ATOM 306 C ILE G 64 31.660 -14.643 20.347 1.00 22.58
ATOM 307 O ILE G 64 31.672 -15.682 19.687 1.00 23.07
ATOM 308 N LYS G 65 32.173 -14.559 21.570 1.00 24.21
ATOM 309 CA LYS G 65 32.425 -15.751 22.374 1.00 25.86
ATOM 310 CB LYS G 65 33.801 -15.682 23.043 1.00 25.90
ATOM 311 CG LYS G 65 34.437 -14.301 23.031 1.00 26.69
ATOM 312 CD LYS G 65 33.621 -13.312 23.847 1.00 28.26
ATOM 313 CE LYS G 65 34.477 -12.614 24.890 1.00 28.67
ATOM 314 NZ LYS G 65 33.661 -12.120 26.034 1.00 28.95
ATOM 315 C LYS G 65 31.329 -15.991 23.413 1.00 26.81
ATOM 316 O LYS G 65 31.299 -15.345 24.461 1.00 26.72
ATOM 317 N GLU G 66 30.491 -16.990 23.149 1.00 27.90
ATOM 318 CA GLU G 66 29.237 -17.188 23.879 1.00 28.82
ATOM 319 CB GLU G 66 28.305 -18.104 23.076 1.00 28.88
ATOM 320 CG GLU G 66 27.621 -19.192 23.895 1.00 30.33
ATOM 321 CD GLU G 66 27.188 -20.381 23.052 1.00 33.17
ATOM 322 OE1 GLU G 66 26.253 -21.098 23.468 1.00 35.05
ATOM 323 OE2 GLU G 66 27.824 -20.634 22.007 1.00 33.14
ATOM 324 C GLU G 66 29.494 -17.783 25.263 1.00 29.12
ATOM 325 O GLU G 66 30.348 -18.655 25.418 1.00 29.28
ATOM 326 N ASN G 67 28.773 -17.301 26.272 1.00 29.32
ATOM 327 CA ASN G 67 29.094 -17.661 27.650 1.00 29.39
ATOM 328 CB ASN G 67 29.462 -16.429 28.477 1.00 29.62
ATOM 329 CG ASN G 67 30.963 -16.231 28.580 1.00 29.84
ATOM 330 OD1 ASN G 67 31.651 -17.000 29.252 1.00 29.93
ATOM 331 ND2 ASN G 67 31.494 -15.324 27.768 1.00 29.22
ATOM 332 C ASN G 67 28.069 -18.540 28.367 1.00 29.15
ATOM 333 O ASN G 67 27.324 -18.070 29.227 1.00 29.06
ATOM 334 N LYS G 68 27.964 -19.788 27.921 1.00 28.87
ATOM 335 CA LYS G 68 27.848 -20.936 28.819 1.00 28.78
ATOM 336 CB LYS G 68 29.127 -21.783 28.771 1.00 28.89 ATOM 337 CG LYS G 68 29.681 -22.003 27.364 1.00 29.26 C
ATOM 338 CD LYS G 68 31.070 -22.631 27.392 1.00 29.68 C
ATOM 339 CE LYS G 68 31.200 -23.648 28.514 1.00 29.46 C
ATOM 340 NZ LYS G 68 32.473 -24.417 28.425 1.00 29.58 N
ATOM 341 C LYS G 68 27.492 -20.555 30.268 1.00 28.60 C
ATOM 342 O LYS G 68 28.346 -20.603 31.154 1.00 28.64 O
ATOM 343 N CYS G 69 26.261 -20.069 30.468 1.00 28.09 N
ATOM 344 CA CYS G 69 25.535 -20.153 31.759 1.00 27.63 C
ATOM 345 CB CYS G 69 25.056 -18.753 32.214 1.00 27.07 C
ATOM 346 SG CYS G 69 23.368 -18.230 31.662 1.00 28.01 S
ATOM 347 C CYS G 69 24.339 -21.120 31.667 1.00 27.69 C
ATOM 348 O CYS G 69 23.967 -21.533 30.570 1.00 27.41 O
ATOM 349 N ASN G 70 23.718 -21.458 32.800 1.00 28.06 N
ATOM 350 CA ASN G 70 22.359 -22.029 32.778 1.00 28.87 C
ATOM 351 CB ASN G 70 22.332 -23.517 33.167 1.00 30.52 C
ATOM 352 CG ASN G 70 23.711 -24.156 33.213 1.00 39.60 C
ATOM 353 OD1 ASN G 70 24.336 -24.404 32.180 1.00 44.97 O
ATOM 354 ND2 ASN G 70 24.204 -24.392 34.429 1.00 51.04 N
ATOM 355 C ASN G 70 21.297 -21.261 33.577 1.00 26.97 C
ATOM 356 O ASN G 70 21.275 -21.320 34.807 1.00 26.50 O
ATOM 357 N GLY G 71 20.320 -20.703 32.866 1.00 25.46 N
ATOM 358 CA GLY G 71 19.231 -19.956 33.496 1.00 23.67 C
ATOM 359 C GLY G 71 17.990 -20.807 33.709 1.00 22.81 C
ATOM 360 O GLY G 71 18.004 -22.008 33.436 1.00 22.79 O
ATOM 361 N TH G 72 16.924 -20.195 34.225 1.00 21.93 N
ATOM 362 CA TH G 72 15.666 -20.910 34.453 1.00 21.30 C
ATOM 363 CB TH G 72 14.737 -20.162 35.441 1.00 21.12 C
ATOM 364 OG1 THR G 72 14.073 -19.090 34.761 1.00 19.87 O
ATOM 365 CG2 THR G 72 15.532 -19.609 36.619 1.00 20.76 C
ATOM 366 C THR G 72 14.923 -21.169 33.139 1.00 21.50 C
ATOM 367 O THR G 72 14.471 -20.236 32.474 1.00 21.85 O
ATOM 368 N ASP G 73 14.797 -22.445 32.781 1.00 21.43 N
ATOM 369 CA ASP G 73 14.514 -22.861 31.404 1.00 21.46 C
ATOM 370 CB ASP G 73 13.109 -22.427 30.971 1.00 21.69 C
ATOM 371 CG ASP G 73 12.794 -22.806 29.529 1.00 22.46 C
ATOM 372 0D1 ASP G 73 13.730 -22.837 28.701 1.00 23.01 O
ATOM 373 OD2 ASP G 73 11.611 -23.068 29.224 1.00 23.09 O
ATOM 374 C ASP G 73 15.561 -22.365 30.406 1.00 20.96 C
ATOM 375 O ASP G 73 15.703 -21.161 30.188 1.00 20.61 O
ATOM 376 N ALA G 74 16.237 -23.305 29.748 1.00 20.42 N
ATOM 377 CA ALA G 74 17.299 -22.967 28.802 1.00 20.38 C
ATOM 378 CB ALA G 74 18.658 -23.365 29.363 1.00 20.11 C
ATOM 379 C ALA G 74 17.092 -23.586 27.421 1.00 20.45 C
ATOM 380 O ALA G 74 18.059 -23.849 26.707 1.00 20.46 O
ATOM 381 N LYS G 75 15.839 -23.747 27.010 1.00 20.67 N
ATOM 382 CA LYS G 75 15.550 -24.031 25.610 1.00 20.99 C
ATOM 383 CB LYS G 75 14.110 -24.512 25.445 1.00 21.20 C
ATOM 384 CG LYS G 75 13.808 -25.810 26.181 1.00 22.02 C
ATOM 385 CD LYS G 75 12.692 -25.624 27.198 1.00 23.66 C
ATOM 386 CE LYS G 75 13.000 -26.348 28.498 1.00 24.93 C
ATOM 387 NZ LYS G 75 12.517 -25.588 29.683 1.00 25.55 N
ATOM 388 C LYS G 75 15.798 -22.788 24.765 1.00 20.92 C
ATOM 389 O LYS G 75 16.187 -22.880 23.600 1.00 20.92 O
ATOM 390 N VAL G 76 15.659 -21.629 25.399 1.00 20.63 N
ATOM 391 CA VAL G 76 16.187 -20.379 24.872 1.00 20.36 C
ATOM 392 CB VAL G 76 15.654 -19.174 25.673 1.00 20.25 C
ATOM 393 CGI VAL G 76 16.330 -17.891 25.215 1.00 20.82 C
ATOM 394 CG2 VAL G 76 14.139 -19.068 25.530 1.00 20.09 C
ATOM 395 C VAL G 76 17.717 -20.356 24.872 1.00 20.29 C
ATOM 396 O VAL G 76 18.353 -20.568 25.905 1.00 20.21 O ATOM 397 N LYS G 77 18.294 -20.039 23.716 1.00 20.17 N
ATOM 398 CA LYS G 77 19.745 -20.018 23.547 1.00 20.17 C
ATOM 399 CB LYS G 77 20.267 -21.419 23.194 1.00 20.62 C
ATOM 400 CG LYS G 77 20.894 -22.180 24.367 1.00 23.31 C
ATOM 401 CD LYS G 77 20.940 -23.684 24.105 1.00 26.74 C
ATOM 402 CE LYS G 77 21.242 -24.468 25.376 1.00 28.32 C
ATOM 403 NZ LYS G 77 21.041 -25.932 25.189 1.00 29.66 N
ATOM 404 C LYS G 77 20.159 -19.010 22.468 1.00 19.45 C
ATOM 405 O LYS G 77 20.754 -19.378 21.453 1.00 19.36 O
ATOM 406 N LEU G 78 19.862 -17.736 22.710 1.00 18.70 N
ATOM 407 CA LEU G 78 19.857 -16.728 21.656 1.00 17.98 C
ATOM 408 CB LEU G 78 19.534 -15.357 22.246 1.00 17.72 C
ATOM 409 CG LEU G 78 18.293 -15.357 23.142 1.00 17.51 C
ATOM 410 CD1 LEU G 78 18.117 -14.023 23.860 1.00 17.41 C
ATOM 411 CD2 LEU G 78 17.045 -15.734 22.349 1.00 17.62 C
ATOM 412 C LEU G 78 21.181 -16.680 20.908 1.00 17.77 C
ATOM 413 O LEU G 78 21.209 -16.672 19.678 1.00 17.89 O
ATOM 414 N ILE G 79 22.273 -16.585 21.657 1.00 17.29 N
ATOM 415 CA ILE G 79 23.592 -16.438 21.058 1.00 17.00 C
ATOM 416 CB ILE G 79 24.691 -16.295 22.126 1.00 16.96 C
ATOM 417 CGI ILE G 79 24.486 -15.011 22.932 1.00 17.21 C
ATOM 418 CD1 ILE G 79 25.529 -14.794 24.009 1.00 17.51 C
ATOM 419 CG2 ILE G 79 26.066 -16.303 21.477 1.00 17.30 C
ATOM 420 C ILE G 79 23.923 -17.616 20.147 1.00 16.83 C
ATOM 421 O ILE G 79 24.307 -17.428 18.992 1.00 17.02 O
ATOM 422 N LYS G 80 23.678 -18.870 20.478 1.00 16.55 N
ATOM 423 CA LYS G 80 24.058 -19.851 19.437 1.00 16.38 C
ATOM 424 CB LYS G 80 23.872 -21.278 19.959 1.00 16.73 C
ATOM 425 CG LYS G 80 24.274 -22.360 18.971 1.00 17.99 C
ATOM 426 CD LYS G 80 25.741 -22.245 18.590 1.00 20.71 C
ATOM 427 CE LYS G 80 26.170 -23.396 17.697 1.00 22.92 C
ATOM 428 NZ LYS G 80 25.352 -23.472 16.454 1.00 24.75 N
ATOM 429 C LYS G 80 23.334 -19.690 18.060 1.00 15.79 C
ATOM 430 O LYS G 80 23.970 -19.700 16.969 1.00 15.32 O
ATOM 431 N GLN G 81 22.019 -19.489 18.112 1.00 15.48 N
ATOM 432 CA GLN G 81 21.192 -19.385 16.905 1.00 15.33 C
ATOM 433 CB GLN G 81 19.711 -19.320 17.287 1.00 15.70 C
ATOM 434 CG GLN G 81 19.269 -20.415 18.242 1.00 17.88 C
ATOM 435 CD GLN G 81 17.848 -20.225 18.734 1.00 20.46 C
ATOM 436 OE1 GLN G 81 17.116 -19.367 18.241 1.00 21.59 O
ATOM 437 NE2 GLN G 81 17.451 -21.028 19.716 1.00 20.26 N
ATOM 438 C GLN G 81 21.546 -18.192 16.019 1.00 14.63 C
ATOM 439 O GLN G 81 21.582 -18.295 14.780 1.00 14.60 O
ATOM 440 N GLU G 82 21.808 -17.057 16.658 1.00 13.81 N
ATOM 441 CA GLU G 82 22.159 -15.854 15.925 1.00 13.37 C
ATOM 442 CB GLU G 82 22.317 -14.664 16.873 1.00 13.20 C
ATOM 443 CG GLU G 82 21.010 -13.984 17.235 1.00 15.04 C
ATOM 444 CD GLU G 82 20.314 -13.388 16.026 1.00 17.51 C
ATOM 445 OE1 GLU G 82 19.726 -12.293 16.154 1.00 18.22 O
ATOM 446 OE2 GLU G 82 20.355 -14.015 14.946 1.00 17.87 O
ATOM 447 C GLU G 82 23.450 -16.101 15.169 1.00 12.99 C
ATOM 448 O GLU G 82 23.584 -15.705 14.014 1.00 12.89 O
ATOM 449 N LEU G 83 24.393 -16.778 15.815 1.00 12.89 N
ATOM 450 CA LEU G 83 25.665 -17.066 15.174 1.00 13.08 C
ATOM 451 CB LEU G 83 26.613 -17.761 16.151 1.00 13.26 C
ATOM 452 CG LEU G 83 26.970 -16.978 17.415 1.00 14.18 C
ATOM 453 CD1 LEU G 83 27.933 -17.774 18.282 1.00 15.11 C
ATOM 454 CD2 LEU G 83 27.557 -15.620 17.059 1.00 14.79 C
ATOM 455 C LEU G 83 25.444 -17.940 13.949 1.00 13.18 C
ATOM 456 O LEU G 83 26.007 -17.673 12.876 1.00 13.05 O ATOM 457 N ASP G 84 24.588 -18.953 14.074 1.00 13.56 N
ATOM 458 CA ASP G 84 24.346 -19.788 12.891 1.00 14.15 C
ATOM 459 CB ASP G 84 23.439 -20.973 13.232 1.00 14.80 C
ATOM 460 CG ASP G 84 24.004 -21.841 14.338 1.00 18.26 C
ATOM 461 0D1 ASP G 84 24.605 -22.891 14.026 1.00 21.11 O
ATOM 462 OD2 ASP G 84 23.837 -21.480 15.520 1.00 22.12 O
ATOM 463 C ASP G 84 23.737 -18.979 11.731 1.00 13.56 C
ATOM 464 O ASP G 84 24.147 -19.111 10.549 1.00 13.70 O
ATOM 465 N LYS G 85 22.780 -18.115 12.068 1.00 12.87 N
ATOM 466 CA LYS G 85 22.128 -17.318 11.033 1.00 12.31 C
ATOM 467 CB LYS G 85 20.987 -16.487 11.619 1.00 12.41 C
ATOM 468 CG LYS G 85 20.087 -15.857 10.568 1.00 12.26 C
ATOM 469 CD LYS G 85 19.083 -14.900 11.189 1.00 12.72 C
ATOM 470 CE LYS G 85 19.772 -13.667 11.750 1.00 14.40 C
ATOM 471 NZ LYS G 85 18.789 -12.676 12.268 1.00 16.45 N
ATOM 472 C LYS G 85 23.147 -16.409 10.353 1.00 11.85 C
ATOM 473 O LYS G 85 23.143 -16.238 9.125 1.00 11.66 O
ATOM 474 N TY G 86 24.031 -15.839 11.165 1.00 11.32 N
ATOM 475 CA TYR G 86 25.051 -14.936 10.665 1.00 11.07 C
ATOM 476 CB TYR G 86 25.863 -14.349 11.820 1.00 11.12 C
ATOM 477 CG TYR G 86 27.216 -13.824 11.399 1.00 11.30 C
ATOM 478 CD1 TYR G 86 27.349 -12.561 10.838 1.00 12.16 C
ATOM 479 CE1 TYR G 86 28.584 -12.080 10.449 1.00 12.39 C
ATOM 480 CZ TYR G 86 29.705 -12.864 10.619 1.00 12.62 C
ATOM 481 OH TYR G 86 30.938 -12.388 10.233 1.00 12.72 O
ATOM 482 CE2 TYR G 86 29.599 -14.121 11.172 1.00 11.38 C
ATOM 483 CD2 TYR G 86 28.360 -14.595 11.558 1.00 11.05 C
ATOM 484 C TYR G 86 25.971 -15.667 9.708 1.00 10.75 C
ATOM 485 O TYR G 86 26.320 -15.140 8.656 1.00 10.45 O
ATOM 486 N LYS G 87 26.343 -16.894 10.053 1.00 10.66 N
ATOM 487 CA LYS G 87 27.220 -17.656 9.174 1.00 11.03 C
ATOM 488 CB LYS G 87 27.588 -18.996 9.813 1.00 11.36 C
ATOM 489 CG LYS G 87 28.300 -18.874 11.149 1.00 12.79 C
ATOM 490 CD LYS G 87 28.627 -20.242 11.722 1.00 14.76 C
ATOM 491 CE LYS G 87 29.336 -20.123 13.060 1.00 15.29 C
ATOM 492 NZ LYS G 87 29.664 -21.460 13.626 1.00 16.27 N
ATOM 493 C LYS G 87 26.541 -17.891 7.826 1.00 10.83 C
ATOM 494 O LYS G 87 27.163 -17.715 6.758 1.00 11.11 O
ATOM 495 N ASN G 88 25.256 -18.243 7.858 1.00 10.52 N
ATOM 496 CA ASN G 88 24.567 -18.464 6.584 1.00 10.21 C
ATOM 497 CB ASN G 88 23.149 -18.989 6.821 1.00 10.61 C
ATOM 498 CG ASN G 88 22.406 -19.271 5.529 1.00 11.81 C
ATOM 499 OD1 ASN G 88 22.998 -19.285 4.450 1.00 12.97 O
ATOM 500 ND2 ASN G 88 21.101 -19.496 5.633 1.00 13.82 N
ATOM 501 C ASN G 88 24.528 -17.187 5.730 1.00 9.42 C
ATOM 502 O ASN G 88 24.780 -17.206 4.500 1.00 8.94 O
ATOM 503 N ALA G 89 24.251 -16.068 6.395 1.00 8.77 N
ATOM 504 CA ALA G 89 24.164 -14.796 5.693 1.00 8.21 C
ATOM 505 CB ALA G 89 23.734 -13.693 6.647 1.00 7.99 C
ATOM 506 C ALA G 89 25.510 -14.465 5.063 1.00 7.78 C
ATOM 507 O ALA G 89 25.586 -13.988 3.927 1.00 7.88 O
ATOM 508 N VAL G 90 26.574 -14.738 5.809 1.00 7.01 N
ATOM 509 CA VAL G 90 27.921 -14.464 5.344 1.00 6.26 C
ATOM 510 CB VAL G 90 28.965 -14.771 6.433 1.00 5.91 C
ATOM 511 CGI VAL G 90 30.361 -14.414 5.945 1.00 5.92 C
ATOM 512 CG2 VAL G 90 28.631 -14.020 7.714 1.00 5.26 C
ATOM 513 C VAL G 90 28.240 -15.284 4.104 1.00 6.25 C
ATOM 514 O VAL G 90 28.798 -14.758 3.144 1.00 6.32 O
ATOM 515 N THR G 91 27.858 -16.558 4.098 1.00 6.24 N
ATOM 516 CA THR G 91 28.129 -17.376 2.915 1.00 6.68 C ATOM 517 CB TH G 91 27.705 -18.840 3.129 1.00 6.62 C
ATOM 518 OG1 TH G 91 28.438 -19.397 4.227 1.00 7.19 O
ATOM 519 CG2 TH G 91 27.971 -19.661 1.876 1.00 7.27 C
ATOM 520 C THR G 91 27.392 -16.808 1.698 1.00 7.02 C
ATOM 521 O THR G 91 27.953 -16.709 0.569 1.00 7.16 O
ATOM 522 N GLU G 92 26.143 -16.402 1.925 1.00 7.31 N
ATOM 523 CA GLU G 92 25.382 -15.849 0.812 1.00 7.81 C
ATOM 524 CB GLU G 92 23.942 -15.547 1.231 1.00 8.23 C
ATOM 525 CG GLU G 92 23.030 -16.761 1.222 1.00 10.91 C
ATOM 526 CD GLU G 92 22.895 -17.372 -0.161 1.00 14.95 C
ATOM 527 OEl GLU G 92 21.801 -17.878 -0.489 1.00 16.14 O
ATOM 528 OE2 GLU G 92 23.884 -17.346 -0.923 1.00 16.53 O
ATOM 529 C GLU G 92 26.053 -14.587 0.267 1.00 7.47 C
ATOM 530 O GLU G 92 26.210 -14.432 -0.947 1.00 7.32 O
ATOM 531 N LEU G 93 26.501 -13.717 1.167 1.00 7.30 N
ATOM 532 CA LEU G 93 27.140 -12.467 0.759 1.00 7.47 C
ATOM 533 CB LEU G 93 27.442 -11.589 1.973 1.00 7.15 C
ATOM 534 CG LEU G 93 26.217 -11.021 2.692 1.00 7.20 C
ATOM 535 CD1 LEU G 93 26.638 -10.123 3.845 1.00 7.93 C
ATOM 536 CD2 LEU G 93 25.325 -10.266 1.716 1.00 6.91 C
ATOM 537 C LEU G 93 28.414 -12.761 -0.020 1.00 7.89 C
ATOM 538 O LEU G 93 28.746 -12.083 -0.991 1.00 7.94 O
ATOM 539 N GLN G 94 29.116 -13.789 0.434 1.00 8.31 N
ATOM 540 CA GLN G 94 30.361 -14.248 -0.160 1.00 9.05 C
ATOM 541 CB GLN G 94 30.985 -15.349 0.701 1.00 9.18 C
ATOM 542 CG GLN G 94 31.324 -14.908 2.114 1.00 10.79 C
ATOM 543 CD GLN G 94 31.993 -16.003 2.920 1.00 13.82 C
ATOM 544 OEl GLN G 94 32.210 -17.109 2.427 1.00 14.98 O
ATOM 545 NE2 GLN G 94 32.324 -15.698 4.170 1.00 15.25 N
ATOM 546 C GLN G 94 30.220 -14.731 -1.603 1.00 9.25 C
ATOM 547 O GLN G 94 31.124 -14.514 -2.410 1.00 9.43 O
ATOM 548 N LEU G 95 29.114 -15.393 -1.941 1.00 9.55 N
ATOM 549 CA LEU G 95 29.003 -15.935 -3.318 1.00 10.17 C
ATOM 550 CB LEU G 95 27.752 -16.811 -3.437 1.00 9.79 C
ATOM 551 CG LEU G 95 27.700 -18.053 -2.545 1.00 8.86 C
ATOM 552 CD1 LEU G 95 26.403 -18.817 -2.764 1.00 8.31 C
ATOM 553 CD2 LEU G 95 28.904 -18.947 -2.798 1.00 7.62 C
ATOM 554 C LEU G 95 29.057 -14.945 -4.528 1.00 11.22 C
ATOM 555 O LEU G 95 29.643 -15.248 -5.567 1.00 11.55 O
ATOM 556 N LEU G 96 28.430 -13.786 -4.361 1.00 12.40 N
ATOM 557 CA LEU G 96 28.142 -12.747 -5.335 1.00 13.66 C
ATOM 558 CB LEU G 96 27.471 -11.548 -4.668 1.00 13.38 C
ATOM 559 CG LEU G 96 26.008 -11.779 -4.288 1.00 13.32 C
ATOM 560 CD1 LEU G 96 25.321 -10.462 -3.975 1.00 12.84 C
ATOM 561 CD2 LEU G 96 25.278 -12.519 -5.397 1.00 13.38 C
ATOM 562 C LEU G 96 29.392 -12.314 -6.094 1.00 14.97 C
ATOM 563 O LEU G 96 29.293 -11.741 -7.178 1.00 15.21 O
ATOM 564 N MET G 97 30.564 -12.678 -5.576 1.00 16.74 N
ATOM 565 CA MET G 97 31.799 -11.956 -5.894 1.00 18.96 C
ATOM 566 CB MET G 97 32.828 -12.102 -4.766 1.00 19.12 C
ATOM 567 CG MET G 97 32.353 -11.577 -3.413 1.00 21.87 C
ATOM 568 SD MET G 97 32.586 -9.794 -3.210 1.00 27.46 S
ATOM 569 CE MET G 97 32.408 -9.214 -4.899 1.00 24.25 C
ATOM 570 C MET G 97 32.408 -12.377 -7.233 1.00 20.09 C
ATOM 571 O MET G 97 33.064 -11.581 -7.905 1.00 20.58 O
ATOM 572 N GLN G 98 32.151 -13.618 -7.634 1.00 21.33 N
ATOM 573 CA GLN G 98 32.735 -14.171 -8.853 1.00 22.21 C
ATOM 574 CB GLN G 98 33.777 -15.243 -8.513 1.00 22.53 C
ATOM 575 CG GLN G 98 34.695 -14.883 -7.347 1.00 23.85 C
ATOM 576 CD GLN G 98 34.172 -15.376 -6.008 1.00 25.21 C ATOM 577 OE1 GLN G 98 33.109 -14.957 -5.549 1.00 24.47
ATOM 578 NE2 GLN G 98 34.939 -16.243 -5.358 1.00 24.85
ATOM 579 C GLN G 98 31.660 -14.756 -9.766 1.00 22.15
ATOM 580 O GLN G 98 30.475 -14.451 -9.624 1.00 21.77
ATOM 581 N PHE G 137 36.645 -13.585 -16.969 1.00 33.25
ATOM 582 CA PHE G 137 35.365 -12.919 -16.764 1.00 36.79
ATOM 583 CB PHE G 137 35.255 -11.672 -17.642 1.00 20.00
ATOM 584 CG PHE G 137 36.265 -10.611 -17.319 1.00 20.00
ATOM 585 CD1 PHE G 137 36.015 -9.677 -16.331 1.00 20.00
ATOM 586 CE1 PHE G 137 36.932 -8.682 -16.050 1.00 20.00
ATOM 587 CZ PHE G 137 38.108 -8.607 -16.766 1.00 20.00
ATOM 588 CE2 PHE G 137 38.362 -9.523 -17.764 1.00 20.00
ATOM 589 CD2 PHE G 137 37.439 -10.510 -18.045 1.00 20.00
ATOM 590 C PHE G 137 34.195 -13.850 -17.063 1.00 48.73
ATOM 591 O PHE G 137 33.039 -13.434 -16.993 1.00 49.28
ATOM 592 N LEU G 138 34.498 -15.040 -17.571 1.00 42.04
ATOM 593 CA LEU G 138 33.471 -16.059 -17.783 1.00 44.26
ATOM 594 CB LEU G 138 34.037 -17.258 -18.553 1.00 20.00
ATOM 595 CG LEU G 138 34.341 -17.114 -20.050 1.00 20.00
ATOM 596 CD1 LEU G 138 34.975 -18.387 -20.605 1.00 20.00
ATOM 597 CD2 LEU G 138 33.095 -16.756 -20.843 1.00 20.00
ATOM 598 C LEU G 138 32.896 -16.527 -16.451 1.00 43.68
ATOM 599 O LEU G 138 31.839 -17.157 -16.406 1.00 50.27
ATOM 600 N GLY G 139 33.614 -16.234 -15.370 1.00 38.56
ATOM 601 CA GLY G 139 33.145 -16.544 -14.022 1.00 47.99
ATOM 602 C GLY G 139 31.826 -15.881 -13.662 1.00 44.53
ATOM 603 O GLY G 139 31.082 -16.383 -12.819 1.00 32.21
ATOM 604 N PHE G 140 31.510 -14.778 -14.337 1.00 46.33
ATOM 605 CA PHE G 140 30.319 -13.992 -14.021 1.00 42.95
ATOM 606 CB PHE G 140 30.530 -12.516 -14.386 1.00 20.00
ATOM 607 CG PHE G 140 31.590 -11.827 -13.564 1.00 20.00
ATOM 608 CD1 PHE G 140 31.295 -11.318 -12.310 1.00 20.00
ATOM 609 CE1 PHE G 140 32.272 -10.683 -11.553 1.00 20.00
ATOM 610 CZ PHE G 140 33.540 -10.511 -12.066 1.00 20.00
ATOM 611 CE2 PHE G 140 33.832 -10.970 -13.334 1.00 20.00
ATOM 612 CD2 PHE G 140 32.851 -11.591 -14.090 1.00 20.00
ATOM 613 C PHE G 140 29.077 -14.525 -14.731 1.00 38.13
ATOM 614 O PHE G 140 27.970 -14.040 -14.504 1.00 57.33
ATOM 615 N LEU G 141 29.271 -15.480 -15.634 1.00 35.20
ATOM 616 CA LEU G 141 28.173 -15.996 -16.446 1.00 27.01
ATOM 617 CB LEU G 141 26.983 -16.392 -15.560 1.00 20.00
ATOM 618 CG LEU G 141 27.185 -17.555 -14.580 1.00 20.00
ATOM 619 CD1 LEU G 141 25.930 -17.779 -13.747 1.00 20.00
ATOM 620 CD2 LEU G 141 27.588 -18.835 -15.306 1.00 20.00
ATOM 621 C LEU G 141 27.750 -14.978 -17.504 1.00 35.79
ATOM 622 O LEU G 141 28.543 -14.613 -18.370 1.00 46.92
ATOM 623 N LEU G 142 26.509 -14.508 -17.424 1.00 38.67
ATOM 624 CA LEU G 142 26.075 -13.372 -18.231 1.00 33.84
ATOM 625 CB LEU G 142 24.737 -13.667 -18.914 1.00 20.00
ATOM 626 CG LEU G 142 24.720 -14.676 -20.063 1.00 20.00
ATOM 627 CD1 LEU G 142 23.339 -14.707 -20.705 1.00 20.00
ATOM 628 CD2 LEU G 142 25.773 -14.324 -21.101 1.00 20.00
ATOM 629 C LEU G 142 25.959 -12.123 -17.368 1.00 36.89
ATOM 630 O LEU G 142 25.257 -12.119 -16.358 1.00 45.42
ATOM 631 N GLY G 143 26.763 -11.115 -17.688 1.00 26.84
ATOM 632 CA GLY G 143 26.817 -9.895 -16.892 1.00 27.41
ATOM 633 C GLY G 143 26.590 -8.645 -17.722 1.00 29.08
ATOM 634 O GLY G 143 26.918 -8.603 -18.908 1.00 40.24
ATOM 635 N VAL G 144 26.026 -7.622 -17.092 1.00 30.17
ATOM 636 CA VAL G 144 25.849 -6.331 -17.739 1.00 34.15 ATOM 637 CB VAL G 144 24.768 -5.496 -17.035 1.00 20.00 C
ATOM 638 CGI VAL G 144 24.730 -4.081 -17.599 1.00 20.00 C
ATOM 639 CG2 VAL G 144 23.414 -6.166 -17.170 1.00 20.00 C
ATOM 640 C VAL G 144 27.152 -5.543 -17.760 1.00 36.67 C
ATOM 641 O VAL G 144 28.104 -5.880 -17.054 1.00 42.49 O
ATOM 642 N GLY G 145 27.185 -4.487 -18.567 1.00 47.09 N
ATOM 643 CA GLY G 145 28.309 -3.563 -18.568 1.00 44.51 C
ATOM 644 C GLY G 145 28.683 -3.184 -17.151 1.00 44.94 C
ATOM 645 O GLY G 145 29.809 -3.424 -16.714 1.00 40.58 O
ATOM 646 N SE G 146 27.732 -2.662 -16.387 1.00 42.06 N
ATOM 647 CA SER G 146 28.033 -2.190 -15.035 1.00 47.39 C
ATOM 648 CB SER G 146 26.797 -1.534 -14.414 1.00 20.00 C
ATOM 649 OG SER G 146 25.719 -2.450 -14.333 1.00 20.00 O
ATOM 650 C SER G 146 28.570 -3.280 -14.101 1.00 51.48 C
ATOM 651 O SER G 146 29.491 -3.034 -13.317 1.00 47.45 O
ATOM 652 N ALA G 147 28.004 -4.480 -14.183 1.00 39.51 N
ATOM 653 CA ALA G 147 28.430 -5.576 -13.316 1.00 43.38 C
ATOM 654 CB ALA G 147 27.531 -6.788 -13.513 1.00 20.00 C
ATOM 655 C ALA G 147 29.894 -5.954 -13.541 1.00 47.39 C
ATOM 656 O ALA G 147 30.635 -6.211 -12.587 1.00 50.18 O
ATOM 657 N ILE G 148 30.309 -5.983 -14.804 1.00 44.67 N
ATOM 658 CA ILE G 148 31.690 -6.311 -15.140 1.00 43.56 C
ATOM 659 CB ILE G 148 31.898 -6.390 -16.663 1.00 20.00 C
ATOM 660 CGI ILE G 148 30.998 -7.469 -17.269 1.00 20.00 C
ATOM 661 CD1 ILE G 148 31.142 -7.612 -18.768 1.00 20.00 C
ATOM 662 CG2 ILE G 148 33.358 -6.663 -16.987 1.00 20.00 C
ATOM 663 C ILE G 148 32.633 -5.265 -14.558 1.00 51.18 C
ATOM 664 O ILE G 148 33.699 -5.592 -14.031 1.00 39.17 O
ATOM 665 N ALA G 149 32.226 -4.003 -14.651 1.00 42.17 N
ATOM 666 CA ALA G 149 33.020 -2.906 -14.116 1.00 36.76 C
ATOM 667 CB ALA G 149 32.386 -1.571 -14.466 1.00 20.00 C
ATOM 668 C ALA G 149 33.150 -3.058 -12.607 1.00 45.19 C
ATOM 669 O ALA G 149 34.222 -2.843 -12.041 1.00 47.83 O
ATOM 670 N SER G 150 32.054 -3.443 -11.961 1.00 43.64 N
ATOM 671 CA SER G 150 32.062 -3.643 -10.518 1.00 43.46 C
ATOM 672 CB SER G 150 30.657 -3.968 -10.010 1.00 20.00 C
ATOM 673 OG SER G 150 30.165 -5.160 -10.596 1.00 20.00 O
ATOM 674 C SER G 150 33.030 -4.762 -10.146 1.00 44.80 C
ATOM 675 O SER G 150 33.774 -4.653 -9.170 1.00 41.55 O
ATOM 676 N GLY G 151 33.025 -5.833 -10.935 1.00 27.01 N
ATOM 677 CA GLY G 151 33.927 -6.946 -10.697 1.00 35.21 C
ATOM 678 C GLY G 151 35.376 -6.519 -10.839 1.00 42.40 C
ATOM 679 O GLY G 151 36.246 -6.924 -10.055 1.00 45.11 O
ATOM 680 N VAL G 152 35.638 -5.691 -11.846 1.00 40.20 N
ATOM 681 CA VAL G 152 36.983 -5.185 -12.076 1.00 46.73 C
ATOM 682 CB VAL G 152 37.056 -4.330 -13.354 1.00 20.00 C
ATOM 683 CGI VAL G 152 38.472 -3.816 -13.568 1.00 20.00 C
ATOM 684 CG2 VAL G 152 36.587 -5.134 -14.557 1.00 20.00 C
ATOM 685 C VAL G 152 37.424 -4.345 -10.885 1.00 48.62 C
ATOM 686 O VAL G 152 38.565 -4.438 -10.432 1.00 49.32 O
ATOM 687 N ALA G 153 36.502 -3.537 -10.370 1.00 35.09 N
ATOM 688 CA ALA G 153 36.788 -2.690 -9.220 1.00 42.37 C
ATOM 689 CB ALA G 153 35.604 -1.787 -8.918 1.00 20.00 C
ATOM 690 C ALA G 153 37.120 -3.557 -8.014 1.00 37.79 C
ATOM 691 O ALA G 153 38.029 -3.247 -7.243 1.00 39.25 O
ATOM 692 N VAL G 154 36.378 -4.648 -7.859 1.00 38.88 N
ATOM 693 CA VAL G 154 36.610 -5.579 -6.763 1.00 35.53 C
ATOM 694 CB VAL G 154 35.549 -6.695 -6.737 1.00 20.00 C
ATOM 695 CGI VAL G 154 35.814 -7.651 -5.584 1.00 20.00 C
ATOM 696 CG2 VAL G 154 34.154 -6.098 -6.634 1.00 20.00 C ATOM 697 C VAL G 154 37.996 -6.209 -6.863 1.00 41.00
ATOM 698 O VAL G 154 38.690 -6.353 -5.856 1.00 50.08
ATOM 699 N SE G 155 38.403 -6.579 -8.075 1.00 37.82
ATOM 700 CA SER G 155 39.733 -7.158 -8.271 1.00 44.68
ATOM 701 CB SER G 155 39.906 -7.630 -9.715 1.00 20.00
ATOM 702 OG SER G 155 39.757 -6.554 -10.625 1.00 20.00
ATOM 703 C SER G 155 40.817 -6.140 -7.914 1.00 41.82
ATOM 704 O SER G 155 41.834 -6.468 -7.304 1.00 49.37
ATOM 705 N LYS G 156 40.566 -4.900 -8.314 1.00 36.99
ATOM 706 CA LYS G 156 41.440 -3.756 -8.097 1.00 35.11
ATOM 707 CB LYS G 156 40.989 -2.562 -8.943 1.00 20.00
ATOM 708 CG LYS G 156 41.146 -2.767 -10.443 1.00 20.00
ATOM 709 CD LYS G 156 40.541 -1.606 -11.227 1.00 20.00
ATOM 710 CE LYS G 156 40.906 -1.679 -12.708 1.00 20.00
ATOM 711 NZ LYS G 156 40.298 -0.569 -13.497 1.00 20.00
ATOM 712 C LYS G 156 41.489 -3.378 -6.620 1.00 35.98
ATOM 713 O LYS G 156 42.501 -2.874 -6.136 1.00 42.31
ATOM 714 N VAL G 157 40.433 -3.719 -5.886 1.00 37.88
ATOM 715 CA VAL G 157 40.341 -3.361 -4.475 1.00 50.94
ATOM 716 CB VAL G 157 38.894 -3.057 -4.061 1.00 20.00
ATOM 717 CGI VAL G 157 38.799 -2.928 -2.551 1.00 20.00
ATOM 718 CG2 VAL G 157 38.403 -1.790 -4.745 1.00 20.00
ATOM 719 C VAL G 157 40.882 -4.474 -3.591 1.00 47.82
ATOM 720 O VAL G 157 41.021 -4.309 -2.379 1.00 56.87
ATOM 721 N LEU G 158 41.279 -5.588 -4.192 1.00 39.52
ATOM 722 CA LEU G 158 41.557 -6.817 -3.448 1.00 50.27
ATOM 723 CB LEU G 158 41.899 -7.952 -4.419 1.00 20.00
ATOM 724 CG LEU G 158 40.817 -8.321 -5.435 1.00 20.00
ATOM 725 CD1 LEU G 158 41.287 -9.458 -6.330 1.00 20.00
ATOM 726 CD2 LEU G 158 39.521 -8.689 -4.729 1.00 20.00
ATOM 727 C LEU G 158 42.627 -6.743 -2.351 1.00 54.47
ATOM 728 O LEU G 158 42.456 -7.343 -1.285 1.00 49.26
ATOM 729 N HIS G 159 43.716 -6.021 -2.585 1.00 59.45
ATOM 730 CA HIS G 159 44.772 -5.947 -1.579 1.00 49.11
ATOM 731 CB HIS G 159 45.963 -5.146 -2.108 1.00 20.00
ATOM 732 CG HIS G 159 46.583 -5.728 -3.340 1.00 20.00
ATOM 733 ND1 HIS G 159 47.606 -6.651 -3.293 1.00 20.00
ATOM 734 CE1 HIS G 159 47.951 -6.984 -4.524 1.00 20.00
ATOM 735 NE2 HIS G 159 47.189 -6.311 -5.368 1.00 20.00
ATOM 736 CD2 HIS G 159 46.325 -5.518 -4.652 1.00 20.00
ATOM 737 C HIS G 159 44.256 -5.325 -0.280 1.00 44.09
ATOM 738 O HIS G 159 44.572 -5.797 0.819 1.00 42.13
ATOM 739 N LEU G 160 43.449 -4.277 -0.410 1.00 37.55
ATOM 740 CA LEU G 160 42.876 -3.609 0.751 1.00 43.52
ATOM 741 CB LEU G 160 42.095 -2.365 0.323 1.00 20.00
ATOM 742 CG LEU G 160 42.891 -1.283 -0.409 1.00 20.00
ATOM 743 CD1 LEU G 160 41.996 -0.107 -0.769 1.00 20.00
ATOM 744 CD2 LEU G 160 44.073 -0.825 0.432 1.00 20.00
ATOM 745 C LEU G 160 41.966 -4.559 1.523 1.00 47.22
ATOM 746 O LEU G 160 41.969 -4.578 2.756 1.00 43.25
ATOM 747 N GLU G 161 41.190 -5.350 0.788 1.00 40.88
ATOM 748 CA GLU G 161 40.292 -6.318 1.402 1.00 40.61
ATOM 749 CB GLU G 161 39.434 -7.005 0.338 1.00 20.00
ATOM 750 CG GLU G 161 38.558 -6.055 -0.462 1.00 20.00
ATOM 751 CD GLU G 161 37.719 -6.773 -1.501 1.00 20.00
ATOM 752 OE1 GLU G 161 36.959 -6.094 -2.224 1.00 20.00
ATOM 753 OE2 GLU G 161 37.819 -8.014 -1.596 1.00 20.00
ATOM 754 C GLU G 161 41.097 -7.352 2.179 1.00 39.76
ATOM 755 O GLU G 161 40.720 -7.747 3.284 1.00 44.02
ATOM 756 N GLY G 162 42.213 -7.781 1.599 1.00 34.18 ATOM 757 CA GLY G 162 43.079 -8.742 2.256 1.00 35.01 C
ATOM 758 C GLY G 162 43.637 -8.163 3.542 1.00 34.86 C
ATOM 759 O GLY G 162 43.706 -8.844 4.570 1.00 47.81 O
ATOM 760 N GLU G 163 44.019 -6.890 3.489 1.00 40.78 N
ATOM 761 CA GLU G 163 44.546 -6.213 4.669 1.00 37.20 C
ATOM 762 CB GLU G 163 45.016 -4.801 4.315 1.00 20.00 C
ATOM 763 CG GLU G 163 46.112 -4.758 3.264 1.00 20.00 C
ATOM 764 CD GLU G 163 46.555 -3.345 2.942 1.00 20.00 C
ATOM 765 OE1 GLU G 163 47.454 -3.181 2.090 1.00 20.00 O
ATOM 766 OE2 GLU G 163 46.003 -2.399 3.540 1.00 20.00 O
ATOM 767 C GLU G 163 43.480 -6.158 5.758 1.00 46.12 C
ATOM 768 O GLU G 163 43.770 -6.363 6.939 1.00 58.66 O
ATOM 769 N VAL G 164 42.243 -5.885 5.354 1.00 42.23 N
ATOM 770 CA VAL G 164 41.129 -5.833 6.292 1.00 35.45 C
ATOM 771 CB VAL G 164 39.827 -5.387 5.602 1.00 20.00 C
ATOM 772 CGI VAL G 164 38.684 -5.343 6.604 1.00 20.00 C
ATOM 773 CG2 VAL G 164 40.015 -4.032 4.937 1.00 20.00 C
ATOM 774 C VAL G 164 40.908 -7.195 6.947 1.00 46.32 C
ATOM 775 O VAL G 164 40.656 -7.284 8.153 1.00 45.08 O
ATOM 776 N ASN G 165 41.011 -8.257 6.151 1.00 40.82 N
ATOM 777 CA ASN G 165 40.854 -9.603 6.687 1.00 46.48 C
ATOM 778 CB ASN G 165 40.897 -10.652 5.573 1.00 20.00 C
ATOM 779 CG ASN G 165 39.710 -10.560 4.634 1.00 20.00 C
ATOM 780 OD1 ASN G 165 38.643 -11.108 4.909 1.00 20.00 O
ATOM 781 ND2 ASN G 165 39.896 -9.881 3.509 1.00 20.00 N
ATOM 782 C ASN G 165 41.947 -9.884 7.708 1.00 50.90 C
ATOM 783 O ASN G 165 41.694 -10.455 8.769 1.00 47.11 O
ATOM 784 N LYS G 166 43.161 -9.451 7.385 1.00 48.36 N
ATOM 785 CA LYS G 166 44.305 -9.640 8.269 1.00 38.71 C
ATOM 786 CB LYS G 166 45.591 -9.154 7.595 1.00 20.00 C
ATOM 787 CG LYS G 166 45.907 -9.850 6.277 1.00 20.00 C
ATOM 788 CD LYS G 166 47.180 -9.298 5.649 1.00 20.00 C
ATOM 789 CE LYS G 166 47.495 -9.990 4.331 1.00 20.00 C
ATOM 790 NZ LYS G 166 48.735 -9.455 3.701 1.00 20.00 N
ATOM 791 C LYS G 166 44.090 -8.907 9.591 1.00 45.07 C
ATOM 792 O LYS G 166 44.459 -9.402 10.657 1.00 56.09 O
ATOM 793 N ILE G 167 43.491 -7.725 9.508 1.00 42.02 N
ATOM 794 CA ILE G 167 43.256 -6.876 10.673 1.00 43.86 C
ATOM 795 CB ILE G 167 43.338 -5.380 10.304 1.00 20.00 C
ATOM 796 CGI ILE G 167 44.721 -5.042 9.743 1.00 20.00 C
ATOM 797 CD1 ILE G 167 44.884 -3.589 9.349 1.00 20.00 C
ATOM 798 CG2 ILE G 167 43.025 -4.514 11.516 1.00 20.00 C
ATOM 799 C ILE G 167 41.921 -7.143 11.377 1.00 49.02 C
ATOM 800 O ILE G 167 41.570 -6.443 12.327 1.00 37.71 O
ATOM 801 N LYS G 168 41.175 -8.142 10.911 1.00 33.87 N
ATOM 802 CA LYS G 168 39.851 -8.426 11.471 1.00 35.11 C
ATOM 803 CB LYS G 168 39.163 -9.533 10.667 1.00 20.00 C
ATOM 804 CG LYS G 168 38.874 -9.175 9.219 1.00 20.00 C
ATOM 805 CD LYS G 168 38.101 -10.286 8.524 1.00 20.00 C
ATOM 806 CE LYS G 168 37.755 -9.909 7.092 1.00 20.00 C
ATOM 807 NZ LYS G 168 36.921 -10.950 6.427 1.00 20.00 N
ATOM 808 C LYS G 168 39.820 -8.790 12.966 1.00 39.27 C
ATOM 809 O LYS G 168 38.932 -8.339 13.690 1.00 32.39 O
ATOM 810 N SE G 169 40.770 -9.599 13.428 1.00 41.30 N
ATOM 811 CA SER G 169 40.805 -10.008 14.827 1.00 43.23 C
ATOM 812 CB SER G 169 42.030 -10.884 15.100 1.00 20.00 C
ATOM 813 OG SER G 169 43.231 -10.175 14.847 1.00 20.00 O
ATOM 814 C SER G 169 40.796 -8.806 15.767 1.00 41.44 C
ATOM 815 O SER G 169 40.016 -8.759 16.718 1.00 44.82 O
ATOM 816 N ALA G 170 41.695 -7.857 15.522 1.00 39.78 N ATOM 817 CA ALA G 170 41.753 -6.638 16.319 1.00 41.01 C
ATOM 818 CB ALA G 170 42.928 -5.775 15.887 1.00 20.00 C
ATOM 819 C ALA G 170 40.448 -5.857 16.211 1.00 46.04 C
ATOM 820 O ALA G 170 39.912 -5.381 17.211 1.00 46.67 O
ATOM 821 N LEU G 171 39.921 -5.766 14.995 1.00 34.26 N
ATOM 822 CA LEU G 171 38.642 -5.108 14.762 1.00 37.69 C
ATOM 823 CB LEU G 171 38.269 -5.179 13.280 1.00 20.00 C
ATOM 824 CG LEU G 171 39.239 -4.485 12.323 1.00 20.00 C
ATOM 825 CD1 LEU G 171 38.764 -4.625 10.881 1.00 20.00 C
ATOM 826 CD2 LEU G 171 39.417 -3.022 12.711 1.00 20.00 C
ATOM 827 C LEU G 171 37.534 -5.723 15.616 1.00 44.67 C
ATOM 828 O LEU G 171 36.683 -5.010 16.151 1.00 34.27 O
ATOM 829 N LEU G 172 37.577 -7.043 15.776 1.00 34.80 N
ATOM 830 CA LEU G 172 36.536 -7.765 16.498 1.00 28.87 C
ATOM 831 CB LEU G 172 36.606 -9.258 16.179 1.00 20.00 C
ATOM 832 CG LEU G 172 36.254 -9.646 14.744 1.00 20.00 C
ATOM 833 CD1 LEU G 172 36.412 -11.143 14.539 1.00 20.00 C
ATOM 834 CD2 LEU G 172 34.842 -9.201 14.414 1.00 20.00 C
ATOM 835 C LEU G 172 36.655 -7.547 18.001 1.00 29.90 C
ATOM 836 O LEU G 172 35.650 -7.435 18.704 1.00 41.09 O
ATOM 837 N SE G 173 37.889 -7.498 18.490 1.00 35.08 N
ATOM 838 CA SER G 173 38.139 -7.406 19.923 1.00 35.53 C
ATOM 839 CB SER G 173 39.578 -7.823 20.245 1.00 20.00 C
ATOM 840 OG SER G 173 40.515 -7.012 19.556 1.00 20.00 O
ATOM 841 C SER G 173 37.860 -5.999 20.450 1.00 35.07 C
ATOM 842 O SER G 173 37.581 -5.815 21.636 1.00 51.28 O
ATOM 843 N THR G 174 37.893 -5.021 19.550 1.00 46.35 N
ATOM 844 CA THR G 174 37.721 -3.621 19.922 1.00 43.83 C
ATOM 845 CB THR G 174 38.341 -2.681 18.860 1.00 20.00 C
ATOM 846 OG1 THR G 174 37.702 -2.897 17.595 1.00 20.00 O
ATOM 847 CG2 THR G 174 39.839 -2.940 18.719 1.00 20.00 C
ATOM 848 C THR G 174 36.236 -3.300 20.083 1.00 52.54 C
ATOM 849 O THR G 174 35.448 -3.528 19.165 1.00 64.10 O
ATOM 850 N ASN G 175 35.839 -2.919 21.295 1.00 55.57 N
ATOM 851 CA ASN G 175 34.501 -2.371 21.528 1.00 40.58 C
ATOM 852 CB ASN G 175 34.109 -2.499 23.005 1.00 20.00 C
ATOM 853 CG ASN G 175 33.819 -3.933 23.416 1.00 20.00 C
ATOM 854 OD1 ASN G 175 33.530 -4.786 22.578 1.00 20.00 O
ATOM 855 ND2 ASN G 175 33.845 -4.190 24.720 1.00 20.00 N
ATOM 856 C ASN G 175 34.404 -0.909 21.089 1.00 43.65 C
ATOM 857 O ASN G 175 35.035 -0.032 21.682 1.00 53.11 O
ATOM 858 N LYS G 176 33.694 -0.671 19.990 1.00 44.89 N
ATOM 859 CA LYS G 176 33.519 0.680 19.463 1.00 46.42 C
ATOM 860 CB LYS G 176 34.847 1.244 18.945 1.00 20.00 C
ATOM 861 CG LYS G 176 35.789 1.756 20.031 1.00 20.00 C
ATOM 862 CD LYS G 176 37.220 1.872 19.511 1.00 20.00 C
ATOM 863 CE LYS G 176 38.243 1.433 20.560 1.00 20.00 C
ATOM 864 NZ LYS G 176 39.542 1.012 19.953 1.00 20.00 N
ATOM 865 C LYS G 176 32.478 0.701 18.352 1.00 45.00 C
ATOM 866 O LYS G 176 32.405 -0.217 17.534 1.00 60.64 O
ATOM 867 N ALA G 177 31.674 1.756 18.330 1.00 46.01 N
ATOM 868 CA ALA G 177 30.717 1.962 17.257 1.00 43.65 C
ATOM 869 CB ALA G 177 29.708 3.027 17.652 1.00 20.00 C
ATOM 870 C ALA G 177 31.437 2.359 15.977 1.00 41.42 C
ATOM 871 O ALA G 177 31.168 1.813 14.907 1.00 45.37 O
ATOM 872 N VAL G 178 32.360 3.308 16.097 1.00 35.70 N
ATOM 873 CA VAL G 178 33.228 3.683 14.987 1.00 43.93 C
ATOM 874 CB VAL G 178 32.876 5.083 14.432 1.00 20.00 C
ATOM 875 CGI VAL G 178 33.896 5.516 13.379 1.00 20.00 C
ATOM 876 CG2 VAL G 178 31.463 5.090 13.860 1.00 20.00 C ATOM 877 C VAL G 178 34.685 3.676 15.427 1.00 34.16 C ATOM 878 O VAL G 178 35.005 4.063 16.550 1.00 44.45 O ATOM 879 N VAL G 179 35.560 3.200 14.550 1.00 44.87 N ATOM 880 CA VAL G 179 36.972 3.080 14.884 1.00 38.47 C ATOM 881 CB VAL G 179 37.255 1.806 15.696 1.00 20.00 C ATOM 882 CGI VAL G 179 38.742 1.679 15.986 1.00 20.00 C ATOM 883 CG2 VAL G 179 36.457 1.817 16.984 1.00 20.00 C ATOM 884 C VAL G 179 37.855 3.091 13.643 1.00 44.79 C ATOM 885 O VAL G 179 37.560 2.423 12.650 1.00 51.88 O ATOM 886 N SE G 180 38.955 3.835 13.719 1.00 45.23 N ATOM 887 CA SE G 180 39.937 3.871 12.643 1.00 48.99 C ATOM 888 CB SER G 180 40.875 5.069 12.812 1.00 20.00 C ATOM 889 OG SER G 180 41.649 4.948 13.993 1.00 20.00 O ATOM 890 C SER G 180 40.740 2.577 12.610 1.00 48.15 C ATOM 891 O SER G 180 41.386 2.212 13.594 1.00 60.42 O ATOM 892 N LEU G 181 40.594 1.827 11.521 1.00 42.42 N ATOM 893 CA LEU G 181 41.389 0.622 11.302 1.00 43.22 C ATOM 894 CB LEU G 181 40.818 -0.190 10.139 1.00 20.00 C ATOM 895 CG LEU G 181 39.415 -0.753 10.350 1.00 20.00 C ATOM 896 CD1 LEU G 181 38.958 -1.514 9.118 1.00 20.00 C ATOM 897 CD2 LEU G 181 39.394 -1.643 11.577 1.00 20.00 C ATOM 898 C LEU G 181 42.838 0.984 11.011 1.00 29.14 C ATOM 899 O LEU G 181 43.144 1.559 9.967 1.00 43.42 O ATOM 900 N SER G 182 43.721 0.695 11.960 1.00 41.83 N ATOM 901 CA SER G 182 45.089 1.186 11.883 1.00 53.52 C ATOM 902 CB SER G 182 45.421 2.069 13.086 1.00 20.00 C ATOM 903 OG SER G 182 45.500 1.303 14.275 1.00 20.00 O ATOM 904 C SER G 182 46.110 0.063 11.741 1.00 44.76 C ATOM 905 O SER G 182 45.995 -0.984 12.379 1.00 37.73 O ATOM 906 N ASN G 183 47.028 0.245 10.799 1.00 47.84 N ATOM 907 CA ASN G 183 48.262 -0.525 10.744 1.00 59.45 C ATOM 908 CB ASN G 183 48.350 -1.276 9.412 1.00 20.00 C ATOM 909 CG ASN G 183 47.312 -2.375 9.290 1.00 20.00 C ATOM 910 OD1 ASN G 183 46.897 -2.964 10.287 1.00 20.00 O ATOM 911 ND2 ASN G 183 46.954 -2.715 8.057 1.00 20.00 N ATOM 912 C ASN G 183 49.445 0.428 10.872 1.00 75.41 C ATOM 913 O ASN G 183 49.386 1.559 10.391 1.00102.31 O ATOM 914 N GLY G 184 50.463 0.021 11.624 1.00 79.30 N ATOM 915 CA GLY G 184 51.584 0.906 11.931 1.00 88.92 C ATOM 916 C GLY G 184 51.464 2.278 11.287 1.00101.85 C ATOM 917 O GLY G 184 51.911 2.485 10.158 1.00113.48 O ATOM 918 N VAL G 185 50.833 3.209 11.999 1.00 86.84 N ATOM 919 CA VAL G 185 50.888 4.635 11.665 1.00 81.80 C ATOM 920 CB VAL G 185 52.336 5.149 11.526 1.00 20.00 C ATOM 921 CGI VAL G 185 52.340 6.607 11.085 1.00 20.00 C ATOM 922 CG2 VAL G 185 53.086 4.984 12.838 1.00 20.00 C ATOM 923 C VAL G 185 50.097 5.027 10.417 1.00 81.69 C ATOM 924 O VAL G 185 50.205 6.157 9.942 1.00 99.84 O ATOM 925 N SER G 186 49.286 4.109 9.902 1.00 70.63 N ATOM 926 CA SER G 186 48.501 4.392 8.705 1.00 72.29 C ATOM 927 CB SER G 186 49.173 3.803 7.463 1.00 20.00 C ATOM 928 OG SER G 186 49.228 2.389 7.534 1.00 20.00 O ATOM 929 C SER G 186 47.066 3.893 8.820 1.00 62.99 C ATOM 930 O SER G 186 46.820 2.769 9.258 1.00 58.35 O ATOM 931 N VAL G 187 46.122 4.736 8.415 1.00 66.49 N ATOM 932 CA VAL G 187 44.709 4.389 8.471 1.00 57.36 C ATOM 933 CB VAL G 187 43.834 5.635 8.704 1.00 20.00 C ATOM 934 CGI VAL G 187 42.371 5.248 8.769 1.00 20.00 C ATOM 935 CG2 VAL G 187 44.254 6.346 9.982 1.00 20.00 C ATOM 936 C VAL G 187 44.266 3.684 7.191 1.00 53.67 C ATOM 937 O VAL G 187 44.408 4.222 6.093 1.00 50.10
ATOM 938 N LEU G 188 43.768 2.460 7.338 1.00 43.20
ATOM 939 CA LEU G 188 43.289 1.678 6.201 1.00 41.76
ATOM 940 CB LEU G 188 43.404 0.183 6.495 1.00 20.00
ATOM 941 CG LEU G 188 44.821 -0.375 6.633 1.00 20.00
ATOM 942 CD1 LEU G 188 44.777 -1.845 7.014 1.00 20.00
ATOM 943 CD2 LEU G 188 45.605 -0.174 5.345 1.00 20.00
ATOM 944 C LEU G 188 41.843 2.021 5.862 1.00 44.75
ATOM 945 O LEU G 188 41.384 1.777 4.746 1.00 45.28
ATOM 946 N TH G 189 41.111 2.500 6.863 1.00 39.28
ATOM 947 CA THR G 189 39.710 2.863 6.694 1.00 36.51
ATOM 948 CB THR G 189 38.985 1.880 5.760 1.00 20.00
ATOM 949 OG1 THR G 189 38.871 0.604 6.400 1.00 20.00
ATOM 950 CG2 THR G 189 39.759 1.715 4.458 1.00 20.00
ATOM 951 C THR G 189 39.006 2.891 8.046 1.00 45.83
ATOM 952 O THR G 189 39.637 3.112 9.079 1.00 42.57
ATOM 953 N SER G 190 37.692 2.695 8.033 1.00 40.44
ATOM 954 CA SER G 190 36.902 2.779 9.255 1.00 41.82
ATOM 955 CB SER G 190 35.919 3.953 9.188 1.00 20.00
ATOM 956 OG SER G 190 34.930 3.737 8.196 1.00 20.00
ATOM 957 C SER G 190 36.153 1.479 9.527 1.00 33.81
ATOM 958 O SER G 190 35.609 0.860 8.611 1.00 49.61
ATOM 959 N LYS G 191 36.134 1.069 10.791 1.00 37.37
ATOM 960 CA LYS G 191 35.365 -0.097 11.208 1.00 41.23
ATOM 961 CB LYS G 191 36.239 -1.047 12.027 1.00 20.00
ATOM 962 CG LYS G 191 37.323 -1.731 11.216 1.00 20.00
ATOM 963 CD LYS G 191 38.193 -2.623 12.085 1.00 20.00
ATOM 964 CE LYS G 191 39.313 -3.257 11.267 1.00 20.00
ATOM 965 NZ LYS G 191 40.316 -3.959 12.119 1.00 20.00
ATOM 966 C LYS G 191 34.143 0.315 12.018 1.00 35.03
ATOM 967 O LYS G 191 34.267 0.958 13.059 1.00 40.06
ATOM 968 N VAL G 192 32.966 -0.093 11.555 1.00 33.70
ATOM 969 CA VAL G 192 31.712 0.327 12.171 1.00 27.61
ATOM 970 CB VAL G 192 30.816 1.081 11.173 1.00 20.00
ATOM 971 CGI VAL G 192 29.505 1.481 11.832 1.00 20.00
ATOM 972 CG2 VAL G 192 31.540 2.293 10.617 1.00 20.00
ATOM 973 C VAL G 192 30.929 -0.857 12.723 1.00 31.74
ATOM 974 O VAL G 192 30.965 -1.954 12.167 1.00 25.58
ATOM 975 N LEU G 193 30.177 -0.610 13.790 1.00 28.88
ATOM 976 CA LEU G 193 29.272 -1.609 14.342 1.00 34.36
ATOM 977 CB LEU G 193 29.940 -2.349 15.504 1.00 20.00
ATOM 978 CG LEU G 193 31.127 -3.249 15.156 1.00 20.00
ATOM 979 CD1 LEU G 193 31.818 -3.743 16.418 1.00 20.00
ATOM 980 CD2 LEU G 193 30.677 -4.419 14.295 1.00 20.00
ATOM 981 C LEU G 193 27.982 -0.950 14.818 1.00 33.03
ATOM 982 O LEU G 193 27.963 -0.290 15.856 1.00 44.93
ATOM 983 N ASP G 194 26.896 -1.170 14.081 1.00 35.09
ATOM 984 CA ASP G 194 25.724 -0.298 14.150 1.00 41.39
ATOM 985 CB ASP G 194 24.766 -0.589 12.995 1.00 20.00
ATOM 986 CG ASP G 194 25.292 -0.090 11.667 1.00 20.00
ATOM 987 OD1 ASP G 194 26.173 0.795 11.668 1.00 20.00
ATOM 988 OD2 ASP G 194 24.863 -0.620 10.621 1.00 20.00
ATOM 989 C ASP G 194 24.976 -0.377 15.479 1.00 38.04
ATOM 990 O ASP G 194 24.097 0.442 15.752 1.00 48.03
ATOM 991 N LEU G 195 25.259 -1.410 16.263 1.00 43.64
ATOM 992 CA LEU G 195 24.463 -1.682 17.449 1.00 35.97
ATOM 993 CB LEU G 195 23.832 -3.071 17.366 1.00 20.00
ATOM 994 CG LEU G 195 22.988 -3.340 16.117 1.00 20.00
ATOM 995 CD1 LEU G 195 22.479 -4.773 16.112 1.00 20.00
ATOM 996 CD2 LEU G 195 21.847 -2.340 15.969 1.00 20.00 ATOM 997 C LEU G 195 25.254 -1.525 18.744 1.00 43.63 C
ATOM 998 O LEU G 195 24.675 -1.495 19.830 1.00 34.71 O
ATOM 999 N ASN G 196 26.558 -1.299 18.617 1.00 44.30 N
ATOM 1000 CA ASN G 196 27.458 -1.365 19.765 1.00 42.38 C
ATOM 1001 CB ASN G 196 28.900 -1.082 19.342 1.00 20.00 C
ATOM 1002 CG ASN G 196 29.508 -2.223 18.551 1.00 20.00 C
ATOM 1003 OD1 ASN G 196 29.101 -3.377 18.688 1.00 20.00 O
ATOM 1004 ND2 ASN G 196 30.503 -1.908 17.731 1.00 20.00 N
ATOM 1005 C ASN G 196 27.041 -0.434 20.900 1.00 43.66 C
ATOM 1006 O ASN G 196 26.944 -0.855 22.053 1.00 33.62 O
ATOM 1007 N ASN G 197 26.706 0.806 20.560 1.00 34.31 N
ATOM 1008 CA ASN G 197 26.346 1.793 21.570 1.00 38.83 C
ATOM 1009 CB ASN G 197 26.089 3.153 20.926 1.00 20.00 C
ATOM 1010 CG ASN G 197 27.362 3.819 20.456 1.00 20.00 C
ATOM 1011 OD1 ASN G 197 28.459 3.458 20.880 1.00 20.00 O
ATOM 1012 ND2 ASN G 197 27.228 4.768 19.541 1.00 20.00 N
ATOM 1013 C ASN G 197 25.139 1.365 22.392 1.00 39.90 C
ATOM 1014 O ASN G 197 25.185 1.357 23.621 1.00 39.04 O
ATOM 1015 N TY G 198 24.065 0.992 21.705 1.00 35.09 N
ATOM 1016 CA TYR G 198 22.875 0.482 22.373 1.00 41.03 C
ATOM 1017 CB TYR G 198 21.804 0.093 21.352 1.00 20.00 C
ATOM 1018 CG TYR G 198 21.274 1.257 20.549 1.00 20.00 C
ATOM 1019 CD1 TYR G 198 20.238 2.041 21.031 1.00 20.00 C
ATOM 1020 CE1 TYR G 198 19.753 3.105 20.299 1.00 20.00 C
ATOM 1021 CZ TYR G 198 20.310 3.398 19.069 1.00 20.00 C
ATOM 1022 OH TYR G 198 19.829 4.450 18.325 1.00 20.00 O
ATOM 1023 CE2 TYR G 198 21.321 2.616 18.559 1.00 20.00 C
ATOM 1024 CD2 TYR G 198 21.799 1.557 19.299 1.00 20.00 C
ATOM 1025 C TYR G 198 23.219 -0.712 23.252 1.00 43.65 C
ATOM 1026 O TYR G 198 22.800 -0.783 24.406 1.00 52.37 O
ATOM 1027 N ILE G 199 24.079 -1.587 22.744 1.00 35.86 N
ATOM 1028 CA ILE G 199 24.490 -2.772 23.486 1.00 45.39 C
ATOM 1029 CB ILE G 199 25.380 -3.704 22.627 1.00 20.00 C
ATOM 1030 CGI ILE G 199 24.556 -4.357 21.512 1.00 20.00 C
ATOM 1031 CD1 ILE G 199 25.365 -5.260 20.598 1.00 20.00 C
ATOM 1032 CG2 ILE G 199 26.037 -4.775 23.487 1.00 20.00 C
ATOM 1033 C ILE G 199 25.210 -2.392 24.779 1.00 37.89 C
ATOM 1034 O ILE G 199 24.808 -2.808 25.865 1.00 45.28 O
ATOM 1035 N ASP G 200 26.185 -1.495 24.669 1.00 37.36 N
ATOM 1036 CA ASP G 200 26.988 -1.098 25.821 1.00 46.66 C
ATOM 1037 CB ASP G 200 28.069 -0.096 25.405 1.00 20.00 C
ATOM 1038 CG ASP G 200 29.216 -0.751 24.660 1.00 20.00 C
ATOM 1039 OD1 ASP G 200 29.360 -1.989 24.751 1.00 20.00 O
ATOM 1040 OD2 ASP G 200 29.996 -0.025 24.009 1.00 20.00 O
ATOM 1041 C ASP G 200 26.109 -0.506 26.916 1.00 51.05 C
ATOM 1042 O ASP G 200 26.370 -0.693 28.105 1.00 57.39 O
ATOM 1043 N LYS G 201 25.004 0.108 26.507 1.00 57.68 N
ATOM 1044 C A LYS G 201 24.104 0.766 27.443 1.00 44.02 C
ATOM 1045 CB LYS G 201 23.138 1.687 26.698 1.00 20.00 C
ATOM 1046 CG LYS G 201 23.815 2.816 25.941 1.00 20.00 C
ATOM 1047 CD LYS G 201 22.797 3.680 25.223 1.00 20.00 C
ATOM 1048 CE LYS G 201 23.464 4.802 24.446 1.00 20.00 C
ATOM 1049 NZ LYS G 201 22.489 5.542 23.596 1.00 20.00 N
ATOM 1050 C LYS G 201 23.325 -0.250 28.274 1.00 43.56 C
ATOM 1051 O LYS G 201 22.868 0.060 29.374 1.00 51.34 O
ATOM 1052 N GLN G 202 23.218 -1.475 27.764 1.00 46.06 N
ATOM 1053 CA GLN G 202 22.308 -2.472 28.333 1.00 44.95 C
ATOM 1054 CB GLN G 202 21.324 -2.975 27.277 1.00 20.00 C
ATOM 1055 CG GLN G 202 20.207 -1.997 26.966 1.00 20.00 C
ATOM 1056 CD GLN G 202 19.339 -2.450 25.809 1.00 20.00 C ATOM 1057 OE1 GLN G 202 19.694 -3.372 25.074 1.00 20.00 O
ATOM 1058 NE2 GLN G 202 18.171 -1.835 25.672 1.00 20.00 N
ATOM 1059 C GLN G 202 23.029 -3.657 28.974 1.00 42.35 C
ATOM 1060 O GLN G 202 22.446 -4.374 29.787 1.00 47.00 O
ATOM 1061 N LEU G 203 24.253 -3.922 28.530 1.00 49.55 N
ATOM 1062 CA LEU G 203 25.003 -5.081 29.008 1.00 50.77 C
ATOM 1063 CB LEU G 203 26.244 -5.322 28.140 1.00 20.00 C
ATOM 1064 CG LEU G 203 26.031 -5.802 26.698 1.00 20.00 C
ATOM 1065 CD1 LEU G 203 27.361 -5.942 25.970 1.00 20.00 C
ATOM 1066 CD2 LEU G 203 25.263 -7.115 26.661 1.00 20.00 C
ATOM 1067 C LEU G 203 25.397 -4.938 30.479 1.00 52.51 C
ATOM 1068 O LEU G 203 25.830 -3.873 30.918 1.00 46.02 O
ATOM 1069 N LEU G 204 25.226 -6.017 31.238 1.00 51.45 N
ATOM 1070 CA LEU G 204 25.644 -6.053 32.635 1.00 58.44 C
ATOM 1071 CB LEU G 204 24.863 -7.127 33.399 1.00 20.00 C
ATOM 1072 CG LEU G 204 23.352 -6.918 33.522 1.00 20.00 C
ATOM 1073 CD1 LEU G 204 22.691 -8.136 34.147 1.00 20.00 C
ATOM 1074 CD2 LEU G 204 23.044 -5.665 34.328 1.00 20.00 C
ATOM 1075 C LEU G 204 27.146 -6.307 32.759 1.00 54.99 C
ATOM 1076 O LEU G 204 27.710 -7.096 31.998 1.00 55.13 O
ATOM 1077 N PRO G 205 27.783 -5.693 33.770 1.00 58.64 N
ATOM 1078 CA PRO G 205 29.236 -5.775 33.842 1.00 52.19 C
ATOM 1079 CB PRO G 205 29.551 -5.040 35.142 1.00 20.00 C
ATOM 1080 CG PRO G 205 28.379 -5.337 36.014 1.00 20.00 C
ATOM 1081 CD PRO G 205 27.182 -5.464 35.099 1.00 20.00 C
ATOM 1082 C PRO G 205 29.647 -7.230 33.970 1.00 54.30 C
ATOM 1083 O PRO G 205 30.783 -7.593 33.663 1.00 70.22 O
ATOM 1084 N ILE G 206 28.709 -8.050 34.430 1.00 62.70 N
ATOM 1085 CA ILE G 206 28.925 -9.480 34.557 1.00 68.19 C
ATOM 1086 CB ILE G 206 29.450 -9.843 35.957 1.00 20.00 C
ATOM 1087 CGI ILE G 206 30.853 -9.269 36.164 1.00 20.00 C
ATOM 1088 CD1 ILE G 206 31.328 -9.317 37.600 1.00 20.00 C
ATOM 1089 CG2 ILE G 206 29.454 -11.352 36.151 1.00 20.00 C
ATOM 1090 C ILE G 206 27.618 -10.223 34.304 1.00 62.35 C
ATOM 1091 O ILE G 206 26.548 -9.772 34.715 1.00 67.16 O
ATOM 1092 N VAL G 207 27.702 -11.314 33.552 1.00 52.22 N
ATOM 1093 CA VAL G 207 26.527 -12.112 33.234 1.00 51.31 C
ATOM 1094 CB VAL G 207 26.414 -12.378 31.722 1.00 20.00 C
ATOM 1095 CGI VAL G 207 25.235 -13.293 31.430 1.00 20.00 C
ATOM 1096 CG2 VAL G 207 26.279 -11.066 30.963 1.00 20.00 C
ATOM 1097 C VAL G 207 26.546 -13.438 33.985 1.00 62.09 C
ATOM 1098 O VAL G 207 27.257 -14.369 33.605 1.00 58.88 O
ATOM 1099 N ASN G 208 25.828 -13.484 35.102 1.00 71.72 N
ATOM 1100 CA ASN G 208 25.723 -14.698 35.900 1.00 70.92 C
ATOM 1101 CB ASN G 208 25.837 -14.370 37.390 1.00 20.00 C
ATOM 1102 CG ASN G 208 27.235 -13.938 37.787 1.00 20.00 C
ATOM 1103 OD1 ASN G 208 28.216 -14.286 37.129 1.00 20.00 O
ATOM 1104 ND2 ASN G 208 27.335 -13.190 38.880 1.00 20.00 N
ATOM 1105 C ASN G 208 24.423 -15.446 35.628 1.00 63.05 C
ATOM 1106 O ASN G 208 23.637 -15.050 34.767 1.00 61.34 O
ATOM 1107 N LYS G 209 24.168 -16.485 36.418 1.00 68.91 N
ATOM 1108 CA LYS G 209 23.006 -17.341 36.212 1.00 59.11 C
ATOM 1109 CB LYS G 209 23.129 -18.620 37.043 1.00 20.00 C
ATOM 1110 CG LYS G 209 24.239 -19.552 36.588 1.00 20.00 C
ATOM 1111 CD LYS G 209 24.335 -20.774 37.486 1.00 20.00 C
ATOM 1112 CE LYS G 209 25.423 -21.724 37.012 1.00 20.00 C
ATOM 1113 NZ LYS G 209 25.548 -22.912 37.901 1.00 20.00 N
ATOM 1114 C LYS G 209 21.696 -16.628 36.539 1.00 50.69 C
ATOM 1115 O LYS G 209 20.616 -17.121 36.212 1.00 51.01 O
ATOM 1116 N GLN G 210 21.792 -15.499 37.235 1.00 44.68 N ATOM 1117 CA GLNG 210 20.621 -14.676 37.518 1.0049.52 C
ATOM 1118 CB GLNG 210 20.828 -13.87438.806 1.0020.00 C
ATOM 1119 CG GLNG210 20.877 -14.71940.070 1.0020.00 C
ATOM 1120 CD GLNG 210 21.149 -13.89341.313 1.0020.00 C
ATOM 1121 OE1 GLNG 210 21.709 -12.80041.237 1.0020.00 O
ATOM 1122 NE2 GLNG 210 20.755 -14.41742.469 1.0020.00 N
ATOM 1123 C GLNG 210 20.336 -13.73036.356 1.0062.08 C
ATOM 1124 O GLNG 210 19.271 -13.785 35.741 1.0080.43 O
ATOM 1125 N SE G211 21.324 -12.905 36.028 1.0058.92 N
ATOM 1126 CA SE G 211 21.231 -11.987 34.898 1.0047.88 C
ATOM 1127 CB SE G 211 22.594 -11.35034.621 1.0020.00 C
ATOM 1128 OG SERG 211 23.553 -12.33434.274 1.0020.00 O
ATOM 1129 C SERG 211 20.722 -12.689 33.642 1.0057.32 C
ATOM 1130 O SERG 211 19.919 -12.133 32.893 1.0050.74 O
ATOM 1131 N CYSG212 21.149 -13.93433.451 1.0044.34 N
ATOM 1132 CA CYSG212 20.890-14.659 32.210 1.0057.52 C
ATOM 1133 CB CYSG212 21.127 -16.18032.363 1.0020.00 C
ATOM 1134 SG CYSG212 22.836 -16.68232.889 1.0020.00 S
ATOM 1135 C CYSG212 19.541 -14.31431.540 1.0060.91 C
ATOM 1136 O CYSG212 19.536 -13.729 30.460 1.0052.17 O
ATOM 1137 N SERG213 18.465 -14.813 32.151 1.0021.55 N
ATOM 1138 CA SERG 213 17.107 -14.631 31.656 1.0021.67 C
ATOM 1139 CB SERG 213 16.133 -15.51232.444 1.0021.81 C
ATOM 1140 OG SERG 213 16.471 -16.88232.323 1.0023.00 O
ATOM 1141 C SERG 213 16.633 -13.188 31.682 1.0021.45 C
ATOM 1142 O SERG 213 16.026 -12.728 30.722 1.0021.98 O
ATOM 1143 N ILEG214 16.856 -12.475 32.783 1.0020.90 N
ATOM 1144 CA ILEG 214 16.585 -11.05032.758 1.0020.45 C
ATOM 1145 CB ILEG 214 16.587 -10.44434.170 1.0020.53 C
ATOM 1146 CGI ILEG 214 15.498 -11.091 35.029 1.0020.46 C
ATOM 1147 CD1 ILEG 214 15.418 -10.535 36.434 1.0021.75 C
ATOM 1148 CG2 ILEG 214 16.393 -8.937 34.103 1.0020.34 C
ATOM 1149 C ILEG 214 17.686-10.409 31.926 1.0020.15 C
ATOM 1150 O ILEG 214 17.435 -9.671 30.968 1.0019.91 O
ATOM 1151 N SERG215 18.918 -10.77032.280 1.0019.84 N
ATOM 1152 CA SERG 215 20.109 -10.297 31.594 1.0019.58 C
ATOM 1153 CB SERG 215 21.369 -10.72232.349 1.0019.76 C
ATOM 1154 OG SERG 215 22.538 -10.269 31.688 1.0019.97 O
ATOM 1155 C SERG 215 20.132 -10.85230.189 1.0019.34 C
ATOM 1156 O SERG215 20.448 -10.15229.230 1.0019.54 O
ATOM 1157 N ASNG216 19.774 -12.125 30.082 1.0018.80 N
ATOM 1158 CA ASNG216 19.738 -12.791 28.798 1.0018.36 C
ATOM 1159 CB ASNG 216 19.394 -14.271 28.966 1.0018.41 C
ATOM 1160 CG ASNG 216 20.426 -15.02029.786 1.0019.55 C
ATOM 1161 OD1 ASNG 216 20.308 -16.227 30.000 1.0020.52 O
ATOM 1162 ND2 ASNG 216 21.445 -14.306 30.250 1.0020.43 N
ATOM 1163 C ASNG 216 18.708 -12.10727.927 1.0017.78 C
ATOM 1164 O ASNG216 18.930 -11.90526.744 1.0017.91 O
ATOM 1165 N ILEG217 17.578 -11.75028.527 1.0017.02 N
ATOM 1166 CA ILEG 217 16.502 -11.08927.804 1.0016.60 C
ATOM 1167 CB ILEG 217 15.247 -10.91628.680 1.0016.46 C
ATOM 1168 CGI ILEG 217 14.608 -12.27528.969 1.0016.26 C
ATOM 1169 CD1 ILEG 217 13.360 -12.19529.822 1.0016.44 C
ATOM 1170 CG2 ILEG 217 14.251 -9.98728.005 1.0016.70 C
ATOM 1171 C ILEG 217 16.953 -9.731 27.297 1.0016.73 C
ATOM 1172 O ILEG 217 16.658 -9.35526.166 1.0016.80 O
ATOM 1173 N GLUG218 17.679 -9.00028.137 1.0017.02 N
ATOM 1174 CA GLUG218 18.177 -7.69227.741 1.0017.70 C
ATOM 1175 CB GLU G 218 18.867 -6.99828.916 1.0018.20 C
ATOM 1176 CG GLU G 218 17.955 -6.748 30.106 1.0021.31 C ATOM 1177 CD GLU G 218 18.652 -6.004 31.228 1.00 25.72 C
ATOM 1178 OE1 GLU G 218 18.016 -5.781 32.279 1.00 26.96 O
ATOM 1179 OE2 GLU G 218 19.834 -5.640 31.058 1.00 27.07 O
ATOM 1180 C GLU G 218 19.144 -7.855 26.578 1.00 17.29 C
ATOM 1181 O GLU G 218 19.123 -7.081 25.617 1.00 17.62 O
ATOM 1182 N TH G 219 19.983 -8.882 26.667 1.00 16.62 N
ATOM 1183 CA THR G 219 20.964 -9.150 25.630 1.00 15.95 C
ATOM 1184 CB THR G 219 21.879 -10.328 26.007 1.00 15.95 C
ATOM 1185 OG1 THR G 219 22.582 -10.021 27.218 1.00 15.63 O
ATOM 1186 CG2 THR G 219 22.884 -10.597 24.897 1.00 15.97 C
ATOM 1187 C THR G 219 20.250 -9.470 24.330 1.00 15.64 C
ATOM 1188 O THR G 219 20.656 -9.022 23.267 1.00 15.93 O
ATOM 1189 N VAL G 220 19.179 -10.248 24.431 1.00 14.98 N
ATOM 1190 CA VAL G 220 18.390 -10.644 23.278 1.00 14.51 C
ATOM 1191 CB VAL G 220 17.285 -11.644 23.665 1.00 14.29 C
ATOM 1192 CGI VAL G 220 16.474 -12.037 22.440 1.00 14.24 C
ATOM 1193 CG2 VAL G 220 17.890 -12.871 24.329 1.00 14.10 C
ATOM 1194 C VAL G 220 17.759 -9.424 22.636 1.00 14.64 C
ATOM 1195 O VAL G 220 17.718 -9.315 21.420 1.00 14.79 O
ATOM 1196 N ILE G 221 17.264 -8.510 23.463 1.00 14.43 N
ATOM 1197 CA ILE G 221 16.658 -7.287 22.959 1.00 14.36 C
ATOM 1198 CB ILE G 221 16.046 -6.448 24.095 1.00 14.03 C
ATOM 1199 CGI ILE G 221 14.955 -7.243 24.816 1.00 13.72 C
ATOM 1200 CD1 ILE G 221 13.820 -7.679 23.914 1.00 14.17 C
ATOM 1201 CG2 ILE G 221 15.487 -5.142 23.550 1.00 13.91 C
ATOM 1202 C ILE G 221 17.700 -6.459 22.222 1.00 14.82 C
ATOM 1203 O ILE G 221 17.427 -5.902 21.158 1.00 14.82 O
ATOM 1204 N GLU G 222 18.901 -6.390 22.788 1.00 15.51 N
ATOM 1205 CA GLU G 222 19.983 -5.640 22.165 1.00 16.52 C
ATOM 1206 CB GLU G 222 21.211 -5.601 23.076 1.00 16.80 C
ATOM 1207 CG GLU G 222 20.971 -4.899 24.403 1.00 19.14 C
ATOM 1208 CD GLU G 222 22.231 -4.780 25.236 1.00 22.62 C
ATOM 1209 OE1 GLU G 222 22.152 -4.246 26.362 1.00 24.35 O
ATOM 1210 OE2 GLU G 222 23.301 -5.219 24.765 1.00 23.98 O
ATOM 1211 C GLU G 222 20.335 -6.269 20.825 1.00 16.65 C
ATOM 1212 O GLU G 222 20.599 -5.574 19.842 1.00 16.95 O
ATOM 1213 N PHE G 223 20.339 -7.597 20.802 1.00 16.70 N
ATOM 1214 CA PHE G 223 20.652 -8.350 19.603 1.00 16.95 C
ATOM 1215 CB PHE G 223 20.705 -9.848 19.904 1.00 16.85 C
ATOM 1216 CG PHE G 223 21.104 -10.689 18.724 1.00 17.23 C
ATOM 1217 CD1 PHE G 223 22.438 -10.954 18.465 1.00 17.98 C
ATOM 1218 CE1 PHE G 223 22.808 -11.727 17.381 1.00 18.28 C
ATOM 1219 CZ PHE G 223 21.842 -12.243 16.541 1.00 18.19 C
ATOM 1220 CE2 PHE G 223 20.508 -11.986 16.788 1.00 18.14 C
ATOM 1221 CD2 PHE G 223 20.144 -11.213 17.874 1.00 17.75 C
ATOM 1222 C PHE G 223 19.610 -8.066 18.540 1.00 17.28 C
ATOM 1223 O PHE G 223 19.945 -7.907 17.382 1.00 17.17 O
ATOM 1224 N GLN G 224 18.348 -8.003 18.948 1.00 17.62 N
ATOM 1225 CA GLN G 224 17.243 -7.712 18.044 1.00 18.16 C
ATOM 1226 CB GLN G 224 15.898 -7.868 18.757 1.00 18.51 C
ATOM 1227 CG GLN G 224 15.586 -9.296 19.178 1.00 20.06 C
ATOM 1228 CD GLN G 224 14.158 -9.465 19.658 1.00 22.03 C
ATOM 1229 OE1 GLN G 224 13.769 -10.539 20.117 1.00 22.15 O
ATOM 1230 NE2 GLN G 224 13.368 -8.403 19.552 1.00 22.11 N
ATOM 1231 C GLN G 224 17.387 -6.309 17.475 1.00 18.04 C
ATOM 1232 O GLN G 224 17.090 -6.068 16.306 1.00 18.17 O
ATOM 1233 N GLN G 225 17.819 -5.382 18.323 1.00 17.90 N
ATOM 1234 CA GLN G 225 18.051 -4.012 17.894 1.00 17.95 C
ATOM 1235 CB GLN G 225 18.389 -3.120 19.090 1.00 18.13 C
ATOM 1236 CG GLN G 225 17.267 -3.006 20.109 1.00 19.04 C ATOM 1237 CD GLN G 225 17.588 -2.034 21.227 1.00 21.22
ATOM 1238 OE1 GLN G 225 18.661 -1.431 21.252 1.00 22.55
ATOM 1239 NE2 GLN G 225 16.656 -1.876 22.159 1.00 22.48
ATOM 1240 C GLN G 225 19.168 -3.958 16.855 1.00 17.84
ATOM 1241 O GLN G 225 19.061 -3.239 15.861 1.00 17.71
ATOM 1242 N LYS G 226 20.235 -4.724 17.077 1.00 17.95
ATOM 1243 CA LYS G 226 21.328 -4.762 16.112 1.00 18.00
ATOM 1244 CB LYS G 226 22.486 -5.613 16.634 1.00 18.21
ATOM 1245 CG LYS G 226 23.157 -5.048 17.875 1.00 18.50
ATOM 1246 CD LYS G 226 24.365 -5.878 18.279 1.00 19.87
ATOM 1247 CE LYS G 226 25.066 -5.278 19.487 1.00 21.36
ATOM 1248 NZ LYS G 226 26.270 -6.061 19.878 1.00 21.83
ATOM 1249 C LYS G 226 20.772 -5.345 14.826 1.00 17.84
ATOM 1250 O LYS G 226 21.062 -4.880 13.723 1.00 17.94
ATOM 1251 N ASN G 227 19.954 -6.374 15.002 1.00 17.70
ATOM 1252 CA ASN G 227 19.238 -7.032 13.932 1.00 17.66
ATOM 1253 CB ASN G 227 18.471 -8.244 14.459 1.00 17.36
ATOM 1254 CG ASN G 227 19.384 -9.296 15.057 1.00 17.40
ATOM 1255 OD1 ASN G 227 18.929 -10.350 15.502 1.00 17.84
ATOM 1256 ND2 ASN G 227 20.682 -9.015 15.070 1.00 17.22
ATOM 1257 C ASN G 227 18.287 -6.028 13.328 1.00 17.76
ATOM 1258 O ASN G 227 18.159 -5.956 12.106 1.00 17.92
ATOM 1259 N ASN G 228 17.627 -5.226 14.164 1.00 17.78
ATOM 1260 CA ASN G 228 16.800 -4.172 13.548 1.00 17.59
ATOM 1261 CB ASN G 228 15.958 -3.344 14.528 1.00 17.89
ATOM 1262 CG ASN G 228 15.101 -2.277 13.809 1.00 18.43
ATOM 1263 OD1 ASN G 228 15.506 -1.119 13.688 1.00 18.74
ATOM 1264 ND2 ASN G 228 13.998 -2.715 13.205 1.00 18.61
ATOM 1265 C ASN G 228 17.603 -3.255 12.662 1.00 17.09
ATOM 1266 O ASN G 228 17.657 -3.466 11.456 1.00 17.17
ATOM 1267 N A G G 229 18.197 -2.211 13.224 1.00 16.33
ATOM 1268 CA ARG G 229 19.046 -1.400 12.381 1.00 15.76
ATOM 1269 CB ARG G 229 19.957 -0.486 13.184 1.00 15.70
ATOM 1270 CG ARG G 229 20.207 0.822 12.468 1.00 14.99
ATOM 1271 CD ARG G 229 21.391 1.555 13.041 1.00 15.33
ATOM 1272 NE ARG G 229 22.116 2.303 12.021 1.00 15.59
ATOM 1273 CZ ARG G 229 23.182 3.053 12.276 1.00 15.85
ATOM 1274 NH1 ARG G 229 23.593 3.214 13.525 1.00 16.20
ATOM 1275 NH2 ARG G 229 23.859 3.614 11.285 1.00 16.63
ATOM 1276 C ARG G 229 19.863 -2.343 11.516 1.00 15.62
ATOM 1277 O ARG G 229 19.671 -2.402 10.304 1.00 15.73
ATOM 1278 N LEU G 230 20.612 -3.225 12.168 1.00 15.46
ATOM 1279 CA LEU G 230 21.409 -4.212 11.454 1.00 15.22
ATOM 1280 CB LEU G 230 22.161 -5.113 12.432 1.00 15.08
ATOM 1281 CG LEU G 230 23.055 -6.187 11.808 1.00 14.70
ATOM 1282 CD1 LEU G 230 24.375 -5.579 11.364 1.00 15.19
ATOM 1283 CD2 LEU G 230 23.300 -7.324 12.791 1.00 15.46
ATOM 1284 C LEU G 230 20.565 -5.055 10.501 1.00 15.31
ATOM 1285 O LEU G 230 20.963 -5.294 9.362 1.00 15.46
ATOM 1286 N LEU G 231 19.444 -5.573 10.997 1.00 15.48
ATOM 1287 CA LEU G 231 18.581 -6.442 10.197 1.00 15.75
ATOM 1288 CB LEU G 231 17.308 -6.793 10.967 1.00 15.90
ATOM 1289 CG LEU G 231 17.482 -7.640 12.226 1.00 16.63
ATOM 1290 CD1 LEU G 231 16.128 -8.049 12.772 1.00 18.45
ATOM 1291 CD2 LEU G 231 18.348 -8.858 11.954 1.00 16.67
ATOM 1292 C LEU G 231 18.210 -5.785 8.872 1.00 15.76
ATOM 1293 O LEU G 231 18.203 -6.432 7.824 1.00 15.84
ATOM 1294 N GLU G 232 17.824 -4.516 8.943 1.00 15.71
ATOM 1295 CA GLU G 232 17.298 -3.811 7.786 1.00 15.93
ATOM 1296 CB GLU G 232 16.537 -2.565 8.229 1.00 16.15 ATOM 1297 CG GLU G 232 15.461 -2.846 9.254 1.00 18.59 C
ATOM 1298 CD GLU G 232 14.077 -2.874 8.644 1.00 21.47 C
ATOM 1299 OE1 GLU G 232 13.964 -3.077 7.415 1.00 22.14 O
ATOM 1300 OE2 GLU G 232 13.100 -2.664 9.393 1.00 23.34 O
ATOM 1301 C GLU G 232 18.399 -3.431 6.806 1.00 15.45 C
ATOM 1302 O GLU G 232 18.169 -3.373 5.601 1.00 15.95 O
ATOM 1303 N ILE G 233 19.594 -3.169 7.323 1.00 14.54 N
ATOM 1304 CA ILE G 233 20.774 -3.128 6.476 1.00 13.69 C
ATOM 1305 CB ILE G 233 22.049 -2.830 7.281 1.00 13.63 C
ATOM 1306 CGI ILE G 233 21.823 -1.640 8.211 1.00 13.58 C
ATOM 1307 CD1 ILE G 233 23.101 -0.917 8.578 1.00 13.55 C
ATOM 1308 CG2 ILE G 233 23.215 -2.543 6.348 1.00 13.88 C
ATOM 1309 C ILE G 233 20.927 -4.450 5.736 1.00 13.28 C
ATOM 1310 O ILE G 233 20.979 -4.473 4.508 1.00 13.04 O
ATOM 1311 N THR G 234 20.758 -5.546 6.469 1.00 13.18 N
ATOM 1312 CA THR G 234 21.038 -6.878 5.940 1.00 13.39 C
ATOM 1313 CB THR G 234 20.839 -7.965 7.015 1.00 13.21 C
ATOM 1314 OGl THR G 234 21.845 -7.836 8.028 1.00 13.15 O
ATOM 1315 CG2 THR G 234 20.916 -9.351 6.394 1.00 13.22 C
ATOM 1316 C THR G 234 20.146 -7.204 4.748 1.00 13.76 C
ATOM 1317 O THR G 234 20.606 -7.766 3.753 1.00 13.95 O
ATOM 1318 N ARG G 235 18.849 -6.966 4.911 1.00 14.26 N
ATOM 1319 CA ARG G 235 17.891 -7.151 3.826 1.00 14.92 C
ATOM 1320 CB ARG G 235 16.463 -6.925 4.328 1.00 15.30 C
ATOM 1321 CG ARG G 235 15.771 -5.712 3.722 1.00 16.27 C
ATOM 1322 CD ARG G 235 14.867 -5.020 4.735 1.00 18.52 C
ATOM 1323 NE ARG G 235 14.345 -5.948 5.734 1.00 17.86 N
ATOM 1324 CZ ARG G 235 13.438 -6.884 5.478 1.00 16.91 C
ATOM 1325 NHl ARG G 235 12.970 -7.035 4.248 1.00 16.59 N
ATOM 1326 NH2 ARG G 235 13.018 -7.687 6.444 1.00 16.86 N
ATOM 1327 C ARG G 235 18.192 -6.211 2.665 1.00 15.05 C
ATOM 1328 O ARG G 235 18.292 -6.640 1.517 1.00 15.15 O
ATOM 1329 N GLU G 236 18.386 -4.935 2.984 1.00 15.18 N
ATOM 1330 CA GLU G 236 18.751 -3.930 1.992 1.00 15.24 C
ATOM 1331 CB GLU G 236 19.179 -2.636 2.687 1.00 15.69 C
ATOM 1332 CG GLU G 236 18.875 -1.369 1.904 1.00 18.22 C
ATOM 1333 CD GLU G 236 19.004 -0.115 2.750 1.00 21.59 C
ATOM 1334 OE1 GLU G 236 19.395 0.937 2.199 1.00 24.41 O
ATOM 1335 OE2 GLU G 236 18.660 -0.168 3.953 1.00 21.59 O
ATOM 1336 C GLU G 236 19.870 -4.421 1.077 1.00 14.61 C
ATOM 1337 O GLU G 236 19.746 -4.377 -0.147 1.00 14.82 O
ATOM 1338 N PHE G 237 20.963 -4.883 1.675 1.00 14.05 N
ATOM 1339 CA PHE G 237 22.110 -5.358 0.907 1.00 13.84 C
ATOM 1340 CB PHE G 237 23.285 -5.682 1.836 1.00 14.04 C
ATOM 1341 CG PHE G 237 24.161 -4.500 2.143 1.00 14.84 C
ATOM 1342 CD 1 PHE G 237 24.412 -4.131 3.454 1.00 15.30 C
ATOM 1343 CE1 PHE G 237 25.268 -3.087 3.743 1.00 15.15 C
ATOM 1344 CZ PHE G 237 25.871 -2.389 2.717 1.00 15.19 C
ATOM 1345 CE2 PHE G 237 25.645 -2.760 1.407 1.00 15.02 C
ATOM 1346 CD2 PHE G 237 24.796 -3.809 1.125 1.00 15.03 C
ATOM 1347 C PHE G 237 21.741 -6.586 0.078 1.00 13.51 C
ATOM 1348 O PHE G 237 22.027 -6.652 -1.117 1.00 13.43 O
ATOM 1349 N SER G 238 21.092 -7.551 0.721 1.00 13.11 N
ATOM 1350 CA SER G 238 20.669 -8.772 0.049 1.00 12.82 C
ATOM 1351 CB SER G 238 19.929 -9.688 1.021 1.00 12.86 C
ATOM 1352 OG SER G 238 20.730 -9.975 2.151 1.00 12.76 O
ATOM 1353 C SER G 238 19.770 -8.444 -1.131 1.00 12.69 C
ATOM 1354 O SER G 238 19.749 -9.165 -2.128 1.00 12.63 O
ATOM 1355 N VAL G 239 19.024 -7.352 -1.010 1.00 12.59 N
ATOM 1356 CA VAL G 239 18.143 -6.916 -2.082 1.00 12.80 C ATOM 1357 CB VAL G 239 17.045 -5.961 -1.578 1.00 12.71 C
ATOM 1358 CGI VAL G 239 16.215 -5.451 -2.747 1.00 13.63 C
ATOM 1359 CG2 VAL G 239 16.157 -6.658 -0.562 1.00 13.57 C
ATOM 1360 C VAL G 239 18.906 -6.242 -3.214 1.00 12.94 C
ATOM 1361 O VAL G 239 18.337 -5.980 -4.273 1.00 13.10 O
ATOM 1362 N ASN G 240 20.173 -5.913 -2.981 1.00 4.15 N
ATOM 1363 CA ASN G 240 20.892 -5.047 -3.909 1.00 4.33 C
ATOM 1364 CB ASN G 240 21.377 -3.779 -3.214 1.00 4.59 C
ATOM 1365 CG ASN G 240 20.260 -2.790 -2.978 1.00 5.36 C
ATOM 1366 ODl ASN G 240 19.681 -2.263 -3.926 1.00 6.27 O
ATOM 1367 ND2 ASN G 240 19.828 -2.683 -1.727 1.00 7.15 N
ATOM 1368 C ASN G 240 22.025 -5.707 -4.689 1.00 4.19 C
ATOM 1369 O ASN G 240 22.565 -5.115 -5.625 1.00 4.19 O
ATOM 1370 N ALA G 241 22.299 -6.970 -4.382 1.00 3.93 N
ATOM 1371 CA ALA G 241 23.459 -7.657 -4.941 1.00 3.90 C
ATOM 1372 CB ALA G 241 23.179 -8.102 -6.368 1.00 3.86 C
ATOM 1373 C ALA G 241 24.702 -6.772 -4.887 1.00 4.22 C
ATOM 1374 O ALA G 241 25.347 -6.532 -5.907 1.00 4.47 O
ATOM 1375 N GLY G 242 24.955 -6.190 -3.719 1.00 4.53 N
ATOM 1376 CA GLY G 242 26.289 -5.717 -3.368 1.00 4.65 C
ATOM 1377 C GLY G 242 26.609 -4.323 -3.872 1.00 4.67 C
ATOM 1378 O GLY G 242 27.770 -3.913 -3.869 1.00 5.27 O
ATOM 1379 N VAL G 243 25.577 -3.570 -4.246 1.00 4.37 N
ATOM 1380 CA VAL G 243 25.750 -2.172 -4.646 1.00 4.32 C
ATOM 1381 CB VAL G 243 26.048 -2.039 -6.153 1.00 3.99 C
ATOM 1382 CGI VAL G 243 26.962 -0.845 -6.414 1.00 4.22 C
ATOM 1383 CG2 VAL G 243 26.649 -3.327 -6.699 1.00 3.85 C
ATOM 1384 C VAL G 243 24.510 -1.342 -4.335 1.00 4.61 C
ATOM 1385 O VAL G 243 23.394 -1.734 -4.673 1.00 4.89 O
ATOM 1386 N THR G 244 24.722 -0.145 -3.801 1.00 4.95 N
ATOM 1387 CA THR G 244 23.615 0.714 -3.408 1.00 5.71 C
ATOM 1388 CB THR G 244 23.475 0.801 -1.879 1.00 6.11 C
ATOM 1389 OGl THR G 244 24.257 -0.228 -1.260 1.00 7.17 O
ATOM 1390 CG2 THR G 244 22.028 0.651 -1.475 1.00 7.55 C
ATOM 1391 C THR G 244 23.802 2.114 -3.967 1.00 5.61 C
ATOM 1392 O THR G 244 24.927 2.590 -4.117 1.00 5.85 O
ATOM 1393 N THR G 245 22.695 2.794 -4.223 1.00 5.53 N
ATOM 1394 CA THR G 245 22.677 4.241 -4.120 1.00 5.81 C
ATOM 1395 CB THR G 245 22.461 4.903 -5.490 1.00 6.13 C
ATOM 1396 OGl THR G 245 23.555 4.575 -6.355 1.00 8.11 O
ATOM 1397 CG2 THR G 245 22.394 6.408 -5.336 1.00 6.63 C
ATOM 1398 C THR G 245 21.609 4.679 -3.126 1.00 5.73 C
ATOM 1399 O THR G 245 20.778 3.869 -2.718 1.00 5.86 O
ATOM 1400 N PRO G 246 21.521 5.993 -2.867 1.00 5.68 N
ATOM 1401 CA PRO G 246 21.893 6.537 -1.574 1.00 5.11 C
ATOM 1402 CB PRO G 246 20.537 6.719 -0.893 1.00 5.19 C
ATOM 1403 CG PRO G 246 19.582 7.023 -2.060 1.00 5.90 C
ATOM 1404 CD PRO G 246 20.305 6.660 -3.353 1.00 6.36 C
ATOM 1405 C PRO G 246 22.831 5.666 -0.743 1.00 4.85 C
ATOM 1406 O PRO G 246 22.663 4.447 -0.677 1.00 5.25 O
ATOM 1407 N VAL G 247 23.900 6.281 -0.249 1.00 4.35 N
ATOM 1408 CA VAL G 247 24.742 5.647 0.749 1.00 3.82 C
ATOM 1409 CB VAL G 247 26.177 6.196 0.717 1.00 3.52 C
ATOM 1410 CGI VAL G 247 27.082 5.352 1.597 1.00 3.62 C
ATOM 1411 CG2 VAL G 247 26.697 6.207 -0.707 1.00 3.60 C
ATOM 1412 C VAL G 247 24.134 5.824 2.131 1.00 3.69 C
ATOM 1413 O VAL G 247 24.038 6.942 2.637 1.00 3.36 O
ATOM 1414 N SER G 248 23.471 4.769 2.588 1.00 3.72 N
ATOM 1415 CA SER G 248 22.676 4.824 3.803 1.00 3.96 C
ATOM 1416 CB SER G 248 22.187 3.427 4.172 1.00 4.07 C ATOM 1417 OG SE G 248 23.188 2.722 4.884 1.00 4.13 O
ATOM 1418 C SER G 248 23.484 5.392 4.959 1.00 4.35 C
ATOM 1419 O SER G 248 24.697 5.201 5.026 1.00 4.36 O
ATOM 1420 N THR G 249 22.776 5.880 5.972 1.00 4.53 N
ATOM 1421 CA THR G 249 23.405 6.259 7.226 1.00 4.61 C
ATOM 1422 CB THR G 249 22.408 6.945 8.175 1.00 4.70 C
ATOM 1423 OG1 THR G 249 21.562 5.959 8.778 1.00 5.42 O
ATOM 1424 CG2 THR G 249 21.553 7.945 7.412 1.00 4.88 C
ATOM 1425 C THR G 249 24.026 5.054 7.925 1.00 4.47 C
ATOM 1426 O THR G 249 24.830 5.210 8.844 1.00 4.74 O
ATOM 1427 N TYR G 250 23.694 3.855 7.454 1.00 4.32 N
ATOM 1428 CA TYR G 250 24.325 2.641 7.968 1.00 4.42 C
ATOM 1429 CB TYR G 250 23.393 1.435 7.845 1.00 4.91 C
ATOM 1430 CG TYR G 250 22.028 1.638 8.462 1.00 6.81 C
ATOM 1431 CD 1 TYR G 250 20.881 1.242 7.790 1.00 8.89 C
ATOM 1432 CE1 TYR G 250 19.631 1.390 8.359 1.00 10.73 C
ATOM 1433 CZ TYR G 250 19.513 1.941 9.622 1.00 12.28 C
ATOM 1434 OH TYR G 250 18.265 2.135 10.172 1.00 12.24 O
ATOM 1435 CE2 TYR G 250 20.640 2.325 10.320 1.00 12.15 C
ATOM 1436 CD2 TYR G 250 21.890 2.148 9.749 1.00 9.81 C
ATOM 1437 C TYR G 250 25.656 2.342 7.285 1.00 4.21 C
ATOM 1438 O TYR G 250 26.539 1.730 7.886 1.00 4.20 O
ATOM 1439 N MET G 251 25.766 2.697 6.007 1.00 4.14 N
ATOM 1440 CA MET G 251 27.045 2.616 5.300 1.00 4.15 C
ATOM 1441 CB MET G 251 26.852 2.798 3.790 1.00 4.14 C
ATOM 1442 CG MET G 251 26.019 1.722 3.123 1.00 4.51 C
ATOM 1443 SD MET G 251 26.772 0.087 3.219 1.00 3.81 S
ATOM 1444 CE MET G 251 25.773 -0.814 2.036 1.00 4.55 C
ATOM 1445 C MET G 251 27.996 3.686 5.816 1.00 4.13 C
ATOM 1446 O MET G 251 29.178 3.427 6.043 1.00 4.24 O
ATOM 1447 N LEU G 252 27.495 4.913 5.886 1.00 4.23 N
ATOM 1448 CA LEU G 252 28.283 6.032 6.369 1.00 4.22 C
ATOM 1449 CB LEU G 252 28.645 6.965 5.215 1.00 4.14 C
ATOM 1450 CG LEU G 252 30.017 6.731 4.581 1.00 4.05 C
ATOM 1451 CD1 LEU G 252 30.513 7.997 3.891 1.00 5.22 C
ATOM 1452 CD2 LEU G 252 31.023 6.242 5.617 1.00 6.20 C
ATOM 1453 C LEU G 252 27.515 6.799 7.432 1.00 4.62 C
ATOM 1454 O LEU G 252 26.389 7.238 7.203 1.00 4.97 O
ATOM 1455 N THR G 253 28.127 6.949 8.600 1.00 4.90 N
ATOM 1456 CA THR G 253 27.659 7.913 9.583 1.00 5.57 C
ATOM 1457 CB THR G 253 28.420 7.769 10.903 1.00 5.55 C
ATOM 1458 OG1 THR G 253 28.440 6.390 11.293 1.00 6.43 O
ATOM 1459 CG2 THR G 253 27.757 8.598 11.988 1.00 6.28 C
ATOM 1460 C THR G 253 27.865 9.329 9.069 1.00 6.03 C
ATOM 1461 O THR G 253 28.888 9.629 8.453 1.00 6.68 O
ATOM 1462 N ASN G 254 26.974 10.230 9.460 1.00 6.39 N
ATOM 1463 CA ASN G 254 27.257 11.649 9.342 1.00 6.79 C
ATOM 1464 CB ASN G 254 26.292 12.459 10.198 1.00 6.85 C
ATOM 1465 CG ASN G 254 26.317 13.927 9.853 1.00 6.81 C
ATOM 1466 OD1 ASN G 254 25.991 14.303 8.728 1.00 7.67 O
ATOM 1467 ND2 ASN G 254 26.919 14.726 10.726 1.00 6.19 N
ATOM 1468 C ASN G 254 28.685 11.958 9.760 1.00 7.08 C
ATOM 1469 O ASN G 254 29.495 12.426 8.961 1.00 6.90 O
ATOM 1470 N SER G 255 28.974 11.718 11.034 1.00 7.21 N
ATOM 1471 CA SER G 255 30.320 11.869 11.561 1.00 7.37 C
ATOM 1472 CB SER G 255 30.477 11.067 12.859 1.00 8.09 C
ATOM 1473 OG SER G 255 29.239 10.928 13.536 1.00 10.47 O
ATOM 1474 C SER G 255 31.365 11.429 10.538 1.00 6.82 C
ATOM 1475 O SER G 255 32.237 12.207 10.150 1.00 6.99 O
ATOM 1476 N GLU G 256 31.240 10.192 10.068 1.00 6.17 N ATOM 1477 CA GLU G 256 32.218 9.629 9.152 1.00 6.13 C
ATOM 1478 CB GLU G 256 31.913 8.158 8.883 1.00 6.22 C
ATOM 1479 CG GLU G 256 32.296 7.240 10.026 1.00 8.41 C
ATOM 1480 CD GLU G 256 31.422 6.006 10.099 1.00 10.26 C
ATOM 1481 OE1 GLU G 256 30.637 5.776 9.156 1.00 11.90 O
ATOM 1482 OE2 GLU G 256 31.532 5.255 11.090 1.00 9.55 O
ATOM 1483 C GLU G 256 32.231 10.401 7.845 1.00 5.76 C
ATOM 1484 O GLU G 256 33.275 10.892 7.418 1.00 5.93 O
ATOM 1485 N LEU G 257 31.075 10.476 7.194 1.00 5.67 N
ATOM 1486 CA LEU G 257 30.972 11.191 5.930 1.00 5.37 C
ATOM 1487 CB LEU G 257 29.512 11.334 5.486 1.00 5.03 C
ATOM 1488 CG LEU G 257 29.282 12.309 4.325 1.00 3.65 C
ATOM 1489 CD1 LEU G 257 29.846 11.755 3.024 1.00 2.00 C
ATOM 1490 CD2 LEU G 257 27.810 12.657 4.172 1.00 2.14 C
ATOM 1491 C LEU G 257 31.623 12.563 6.048 1.00 5.64 C
ATOM 1492 O LEU G 257 32.401 12.970 5.185 1.00 5.81 O
ATOM 1493 N LEU G 258 31.353 13.249 7.153 1.00 5.75 N
ATOM 1494 CA LEU G 258 31.792 14.629 7.301 1.00 5.91 C
ATOM 1495 CB LEU G 258 31.162 15.276 8.535 1.00 6.10 C
ATOM 1496 CG LEU G 258 29.897 16.091 8.256 1.00 5.75 C
ATOM 1497 CD1 LEU G 258 29.230 16.525 9.552 1.00 6.33 C
ATOM 1498 CD2 LEU G 258 30.219 17.294 7.385 1.00 7.33 C
ATOM 1499 C LEU G 258 33.315 14.758 7.331 1.00 6.03 C
ATOM 1500 O LEU G 258 33.874 15.664 6.713 1.00 5.73 O
ATOM 1501 N SE G 259 33.983 13.867 8.061 1.00 6.47 N
ATOM 1502 CA SER G 259 35.442 13.887 8.139 1.00 6.95 C
ATOM 1503 CB SER G 259 35.929 13.137 9.381 1.00 7.05 C
ATOM 1504 OG SER G 259 36.284 11.802 9.064 1.00 6.86 O
ATOM 1505 C SER G 259 36.060 13.284 6.883 1.00 6.74 C
ATOM 1506 O SER G 259 37.173 13.638 6.493 1.00 6.86 O
ATOM 1507 N LEU G 260 35.311 12.400 6.234 1.00 6.31 N
ATOM 1508 CA LEU G 260 35.715 11.854 4.946 1.00 6.09 C
ATOM 1509 CB LEU G 260 34.747 10.756 4.507 1.00 6.09 C
ATOM 1510 CG LEU G 260 35.306 9.334 4.473 1.00 6.24 C
ATOM 1511 CD1 LEU G 260 34.338 8.388 3.779 1.00 6.53 C
ATOM 1512 CD2 LEU G 260 36.663 9.309 3.790 1.00 5.98 C
ATOM 1513 C LEU G 260 35.775 12.947 3.887 1.00 6.25 C
ATOM 1514 O LEU G 260 36.696 12.982 3.072 1.00 6.37 O
ATOM 1515 N ILE G 261 34.724 13.760 3.826 1.00 6.63 N
ATOM 1516 CA ILE G 261 34.729 14.952 2.987 1.00 7.19 C
ATOM 1517 CB ILE G 261 33.504 15.840 3.262 1.00 7.09 C
ATOM 1518 CG1 ILE G 261 32.292 15.350 2.474 1.00 7.46 C
ATOM 1519 CD1 ILE G 261 30.991 15.952 2.951 1.00 8.38 C
ATOM 1520 CG2 ILE G 261 33.809 17.290 2.916 1.00 6.61 C
ATOM 1521 C ILE G 261 35.966 15.768 3.307 1.00 8.01 C
ATOM 1522 O ILE G 261 36.716 16.162 2.414 1.00 8.26 O
ATOM 1523 N ASN G 262 36.157 16.040 4.592 1.00 9.05 N
ATOM 1524 CA ASN G 262 37.337 16.748 5.049 1.00 9.88 C
ATOM 1525 CB ASN G 262 37.517 16.575 6.555 1.00 9.99 C
ATOM 1526 CG ASN G 262 38.185 17.770 7.197 1.00 11.16 C
ATOM 1527 OD1 ASN G 262 38.493 18.756 6.526 1.00 12.70 O
ATOM 1528 ND2 ASN G 262 38.391 17.701 8.506 1.00 13.20 N
ATOM 1529 C ASN G 262 38.585 16.282 4.316 1.00 10.17 C
ATOM 1530 O ASN G 262 39.426 17.093 3.928 1.00 10.52 O
ATOM 1531 N ASP G 263 38.684 14.976 4.094 1.00 10.62 N
ATOM 1532 CA ASP G 263 39.925 14.380 3.621 1.00 11.02 C
ATOM 1533 CB ASP G 263 40.022 12.917 4.055 1.00 11.49 C
ATOM 1534 CG ASP G 263 41.297 12.251 3.577 1.00 12.80 C
ATOM 1535 OD1 ASP G 263 42.377 12.863 3.715 1.00 14.72 O
ATOM 1536 OD2 ASP G 263 41.220 11.113 3.068 1.00 13.88 O ATOM 1537 C ASP G 263 40.067 14.491 2.107 1.00 10.92 C
ATOM 1538 O ASP G 263 41.135 14.224 1.556 1.00 10.96 O
ATOM 1539 N MET G 264 39.003 14.931 1.442 1.00 10.91 N
ATOM 1540 CA MET G 264 38.989 14.992 -0.015 1.00 10.78 C
ATOM 1541 CB MET G 264 37.557 15.121 -0.534 1.00 10.51 C
ATOM 1542 CG MET G 264 36.669 13.937 -0.194 1.00 11.26 C
ATOM 1543 SD MET G 264 35.025 14.078 -0.916 1.00 12.70 S
ATOM 1544 CE MET G 264 34.634 15.778 -0.513 1.00 13.92 C
ATOM 1545 C MET G 264 39.851 16.135 -0.543 1.00 10.85 C
ATOM 1546 O MET G 264 39.830 17.238 0.002 1.00 11.03 O
ATOM 1547 N PRO G 265 40.626 15.863 -1.604 1.00 10.88 N
ATOM 1548 CA PRO G 265 41.558 16.827 -2.184 1.00 11.09 C
ATOM 1549 CB PRO G 265 42.357 15.986 -3.188 1.00 11.28 C
ATOM 1550 CG PRO G 265 41.513 14.787 -3.453 1.00 11.24 C
ATOM 1551 CD PRO G 265 40.807 14.515 -2.167 1.00 11.03 C
ATOM 1552 C PRO G 265 40.845 17.965 -2.908 1.00 11.19 C
ATOM 1553 O PRO G 265 41.070 18.175 -4.100 1.00 11.47 O
ATOM 1554 N ILE G 266 40.053 18.739 -2.173 1.00 11.54 N
ATOM 1555 CA ILE G 266 39.282 19.820 -2.777 1.00 12.15 C
ATOM 1556 CB ILE G 266 37.792 19.454 -2.914 1.00 12.22 C
ATOM 1557 CGI ILE G 266 37.245 18.928 -1.585 1.00 12.53 C
ATOM 1558 CD1 ILE G 266 35.733 18.918 -1.510 1.00 12.40 C
ATOM 1559 CG2 ILE G 266 37.594 18.431 -4.023 1.00 12.74 C
ATOM 1560 C ILE G 266 39.413 21.132 -2.013 1.00 12.29 C
ATOM 1561 O ILE G 266 39.853 21.156 -0.863 1.00 12.36 O
ATOM 1562 N THR G 267 39.034 22.223 -2.670 1.00 12.29 N
ATOM 1563 CA THR G 267 39.039 23.541 -2.050 1.00 12.43 C
ATOM 1564 CB THR G 267 38.564 24.627 -3.034 1.00 12.40 C
ATOM 1565 OGl THR G 267 37.340 25.204 -2.562 1.00 13.21 O
ATOM 1566 CG2 THR G 267 38.341 24.033 -4.417 1.00 12.21 C
ATOM 1567 C THR G 267 38.141 23.560 -0.819 1.00 12.37 C
ATOM 1568 O THR G 267 37.440 22.589 -0.537 1.00 12.29 O
ATOM 1569 N ASN G 268 38.174 24.664 -0.081 1.00 12.47 N
ATOM 1570 CA ASN G 268 37.523 24.720 1.219 1.00 12.57 C
ATOM 1571 CB ASN G 268 38.199 25.751 2.121 1.00 12.69 C
ATOM 1572 CG ASN G 268 39.221 25.127 3.048 1.00 13.65 C
ATOM 1573 ODl ASN G 268 39.463 23.921 3.000 1.00 14.37 O
ATOM 1574 ND2 ASN G 268 39.843 25.949 3.884 1.00 15.74 N
ATOM 1575 C ASN G 268 36.028 24.995 1.123 1.00 12.43 C
ATOM 1576 O ASN G 268 35.232 24.403 1.853 1.00 12.51 O
ATOM 1577 N ASP G 269 35.655 25.926 0.252 1.00 12.34 N
ATOM 1578 CA ASP G 269 34.248 26.218 0.008 1.00 12.33 C
ATOM 1579 CB ASP G 269 34.106 27.359 -0.999 1.00 12.89 C
ATOM 1580 CG ASP G 269 34.761 28.639 -0.525 1.00 14.84 C
ATOM 1581 ODl ASP G 269 34.594 28.989 0.663 1.00 16.90 O
ATOM 1582 OD2 ASP G 269 35.473 29.277 -1.328 1.00 17.65 O
ATOM 1583 C ASP G 269 33.532 24.978 -0.506 1.00 11.60 C
ATOM 1584 O ASP G 269 32.411 24.679 -0.095 1.00 11.65 O
ATOM 1585 N GLN G 270 34.189 24.260 -1.410 1.00 10.62 N
ATOM 1586 CA GLN G 270 33.728 22.943 -1.816 1.00 10.01 C
ATOM 1587 CB GLN G 270 34.795 22.236 -2.647 1.00 10.18 C
ATOM 1588 CG GLN G 270 34.248 21.533 -3.870 1.00 11.49 C
ATOM 1589 CD GLN G 270 35.200 21.598 -5.043 1.00 14.38 C
ATOM 1590 OE1 GLN G 270 35.516 20.579 -5.655 1.00 16.38 O
ATOM 1591 NE2 GLN G 270 35.718 22.789 -5.318 1.00 15.41 N
ATOM 1592 C GLN G 270 33.366 22.094 -0.606 1.00 9.48 C
ATOM 1593 O GLN G 270 32.213 21.698 -0.437 1.00 9.12 O
ATOM 1594 N LYS G 271 34.358 21.809 0.231 1.00 9.19 N
ATOM 1595 CA LYS G 271 34.126 21.040 1.445 1.00 8.89 C
ATOM 1596 CB LYS G 271 35.362 21.070 2.345 1.00 8.52 C ATOM 1597 CG LYS G 271 36.541 20.285 1.797 1.00 9.14 C
ATOM 1598 CD LYS G 271 37.643 20.147 2.832 1.00 10.72 C
ATOM 1599 CE LYS G 271 39.013 20.137 2.176 1.00 10.79 C
ATOM 1600 NZ LYS G 271 40.035 19.472 3.030 1.00 9.77 N
ATOM 1601 C LYS G 271 32.907 21.563 2.199 1.00 8.83 C
ATOM 1602 O LYS G 271 31.959 20.820 2.452 1.00 9.05 O
ATOM 1603 N LYS G 272 32.899 22.863 2.474 1.00 8.65 N
ATOM 1604 CA LYS G 272 31.789 23.482 3.187 1.00 8.50 C
ATOM 1605 CB LYS G 272 31.997 24.992 3.304 1.00 9.14 C
ATOM 1606 CG LYS G 272 30.762 25.748 3.766 1.00 11.58 C
ATOM 1607 CD LYS G 272 30.925 27.246 3.575 1.00 15.78 C
ATOM 1608 CE LYS G 272 29.995 28.021 4.492 1.00 17.65 C
ATOM 1609 NZ LYS G 272 30.462 29.418 4.703 1.00 19.68 N
ATOM 1610 C LYS G 272 30.458 23.191 2.503 1.00 7.88 C
ATOM 1611 O LYS G 272 29.486 22.808 3.154 1.00 8.12 O
ATOM 1612 N LEU G 273 30.408 23.416 1.194 1.00 6.95 N
ATOM 1613 CA LEU G 273 29.217 23.104 0.413 1.00 5.70 C
ATOM 1614 CB LEU G 273 29.469 23.344 -1.077 1.00 5.85 C
ATOM 1615 CG LEU G 273 28.313 23.000 -2.020 1.00 4.65 C
ATOM 1616 CD1 LEU G 273 27.277 24.114 -2.032 1.00 4.57 C
ATOM 1617 CD2 LEU G 273 28.829 22.729 -3.425 1.00 3.69 C
ATOM 1618 C LEU G 273 28.781 21.663 0.644 1.00 5.14 C
ATOM 1619 O LEU G 273 27.678 21.409 1.128 1.00 5.25 O
ATOM 1620 N MET G 274 29.665 20.724 0.327 1.00 4.52 N
ATOM 1621 CA MET G 274 29.354 19.312 0.482 1.00 4.59 C
ATOM 1622 CB MET G 274 30.573 18.454 0.152 1.00 4.35 C
ATOM 1623 CG MET G 274 30.938 18.457 -1.319 1.00 4.50 C
ATOM 1624 SD MET G 274 32.305 17.344 -1.679 1.00 5.51 S
ATOM 1625 CE MET G 274 31.469 15.758 -1.633 1.00 5.26 C
ATOM 1626 C MET G 274 28.864 19.014 1.893 1.00 5.18 C
ATOM 1627 O MET G 274 27.893 18.280 2.075 1.00 5.61 O
ATOM 1628 N SE G 275 29.457 19.689 2.875 1.00 5.89 N
ATOM 1629 CA SER G 275 29.118 19.465 4.278 1.00 6.18 C
ATOM 1630 CB SER G 275 30.161 20.108 5.194 1.00 6.33 C
ATOM 1631 OG SER G 275 31.457 19.601 4.925 1.00 5.91 O
ATOM 1632 C SER G 275 27.726 19.989 4.619 1.00 6.58 C
ATOM 1633 O SER G 275 27.031 19.425 5.464 1.00 7.03 O
ATOM 1634 N ASN G 276 27.313 21.054 3.940 1.00 7.07 N
ATOM 1635 CA ASN G 276 25.979 21.606 4.140 1.00 7.86 C
ATOM 1636 CB ASN G 276 25.987 23.126 3.942 1.00 8.34 C
ATOM 1637 CG ASN G 276 26.343 23.881 5.214 1.00 9.77 C
ATOM 1638 ODl ASN G 276 26.033 23.439 6.320 1.00 11.84 O
ATOM 1639 ND2 ASN G 276 26.964 25.044 5.057 1.00 11.15 N
ATOM 1640 C ASN G 276 24.908 20.954 3.262 1.00 7.71 C
ATOM 1641 O ASN G 276 23.780 21.442 3.191 1.00 7.84 O
ATOM 1642 N ASN G 277 25.239 19.819 2.649 1.00 7.77 N
ATOM 1643 CA ASN G 277 24.372 19.220 1.631 1.00 7.85 C
ATOM 1644 CB ASN G 277 24.704 19.777 0.246 1.00 7.58 C
ATOM 1645 CG ASN G 277 24.023 21.099 -0.027 1.00 8.29 C
ATOM 1646 ODl ASN G 277 22.818 21.152 -0.272 1.00 9.04 O
ATOM 1647 ND2 ASN G 277 24.798 22.176 -0.008 1.00 9.57 N
ATOM 1648 C ASN G 277 24.410 17.693 1.590 1.00 7.86 C
ATOM 1649 O ASN G 277 24.154 17.089 0.549 1.00 7.85 O
ATOM 1650 N VAL G 278 24.886 17.093 2.674 1.00 7.67 N
ATOM 1651 CA VAL G 278 24.839 15.645 2.879 1.00 7.77 C
ATOM 1652 CB VAL G 278 24.594 15.309 4.352 1.00 7.98 C
ATOM 1653 CGI VAL G 278 25.915 15.261 5.100 1.00 7.21 C
ATOM 1654 CG2 VAL G 278 23.655 16.332 4.977 1.00 8.99 C
ATOM 1655 C VAL G 278 23.843 14.865 2.019 1.00 7.76 C
ATOM 1656 O VAL G 278 24.183 13.811 1.483 1.00 7.84 O ATOM 1657 N GLN G 279 22.569 15.228 2.118 1.00 7.47 N
ATOM 1658 CA GLN G 279 21.510 14.444 1.492 1.00 7.07 C
ATOM 1659 CB GLN G 279 20.187 15.204 1.550 1.00 7.62 C
ATOM 1660 CG GLN G 279 19.021 14.376 2.044 1.00 10.35 C
ATOM 1661 CD GLN G 279 17.682 14.997 1.702 1.00 13.70 C
ATOM 1662 OE1 GLN G 279 17.612 16.002 0.996 1.00 15.06 O
ATOM 1663 NE2 GLN G 279 16.607 14.383 2.179 1.00 13.97 N
ATOM 1664 C GLN G 279 21.852 14.121 0.042 1.00 6.02 C
ATOM 1665 O GLN G 279 22.032 12.958 -0.323 1.00 5.45 O
ATOM 1666 N ILE G 280 21.863 15.154 -0.792 1.00 5.25 N
ATOM 1667 CA ILE G 280 22.325 15.034 -2.169 1.00 4.74 C
ATOM 1668 CB ILE G 280 22.650 16.408 -2.771 1.00 4.58 C
ATOM 1669 CGI ILE G 280 21.527 17.396 -2.461 1.00 4.16 C
ATOM 1670 CD1 ILE G 280 20.235 17.078 -3.177 1.00 3.88 C
ATOM 1671 CG2 ILE G 280 22.835 16.293 -4.271 1.00 3.92 C
ATOM 1672 C ILE G 280 23.550 14.135 -2.286 1.00 4.43 C
ATOM 1673 O ILE G 280 23.493 13.081 -2.917 1.00 4.39 O
ATOM 1674 N VAL G 281 24.676 14.596 -1.749 1.00 4.05 N
ATOM 1675 CA VAL G 281 25.906 13.816 -1.795 1.00 3.58 C
ATOM 1676 CB VAL G 281 26.918 14.251 -0.714 1.00 3.13 C
ATOM 1677 CGI VAL G 281 28.296 13.684 -1.026 1.00 2.34 C
ATOM 1678 CG2 VAL G 281 26.978 15.768 -0.616 1.00 2.21 C
ATOM 1679 C VAL G 281 25.593 12.335 -1.626 1.00 3.96 C
ATOM 1680 O VAL G 281 25.875 11.534 -2.515 1.00 4.15 O
ATOM 1681 N ARG G 282 24.908 11.994 -0.539 1.00 4.23 N
ATOM 1682 CA ARG G 282 24.500 10.615 -0.296 1.00 4.45 C
ATOM 1683 CB ARG G 282 23.570 10.540 0.911 1.00 3.96 C
ATOM 1684 CG ARG G 282 24.225 10.953 2.203 1.00 2.99 C
ATOM 1685 CD ARG G 282 23.924 9.962 3.303 1.00 2.28 C
ATOM 1686 NE ARG G 282 24.332 10.474 4.605 1.00 2.00 N
ATOM 1687 CZ ARG G 282 25.026 9.777 5.498 1.00 2.44 C
ATOM 1688 NHl ARG G 282 25.359 8.517 5.251 1.00 2.04 N
ATOM 1689 NH2 ARG G 282 25.369 10.333 6.650 1.00 3.44 N
ATOM 1690 C ARG G 282 23.798 10.039 -1.516 1.00 5.32 C
ATOM 1691 O ARG G 282 24.143 8.958 -1.997 1.00 5.95 O
ATOM 1692 N GLN G 283 22.800 10.765 -2.006 1.00 5.50 N
ATOM 1693 CA GLN G 283 22.045 10.327 -3.169 1.00 5.80 C
ATOM 1694 CB GLN G 283 20.910 11.303 -3.471 1.00 6.19 C
ATOM 1695 CG GLN G 283 19.768 11.219 -2.480 1.00 9.68 C
ATOM 1696 CD GLN G 283 18.840 12.406 -2.561 1.00 13.92 C
ATOM 1697 OE1 GLN G 283 18.991 13.269 -3.426 1.00 16.20 O
ATOM 1698 NE2 GLN G 283 17.833 12.428 -1.696 1.00 14.17 N
ATOM 1699 C GLN G 283 22.953 10.175 -4.379 1.00 5.44 C
ATOM 1700 O GLN G 283 22.687 9.364 -5.264 1.00 5.43 O
ATOM 1701 N GLN G 284 24.067 10.896 -4.371 1.00 5.26 N
ATOM 1702 CA GLN G 284 24.957 10.920 -5.521 1.00 5.18 C
ATOM 1703 CB GLN G 284 25.568 12.307 -5.702 1.00 5.32 C
ATOM 1704 CG GLN G 284 24.813 13.189 -6.673 1.00 6.85 C
ATOM 1705 CD GLN G 284 25.434 14.560 -6.804 1.00 9.21 C
ATOM 1706 OE1 GLN G 284 25.863 15.160 -5.819 1.00 9.74 O
ATOM 1707 NE2 GLN G 284 25.492 15.064 -8.027 1.00 9.79 N
ATOM 1708 C GLN G 284 26.060 9.882 -5.400 1.00 4.67 C
ATOM 1709 O GLN G 284 26.884 9.736 -6.302 1.00 4.19 O
ATOM 1710 N SER G 285 26.109 9.199 -4.262 1.00 4.51 N
ATOM 1711 CA SER G 285 27.204 8.281 -3.990 1.00 4.39 C
ATOM 1712 CB SER G 285 27.767 8.510 -2.587 1.00 4.13 C
ATOM 1713 OG SER G 285 28.180 9.856 -2.421 1.00 4.40 O
ATOM 1714 C SER G 285 26.767 6.834 -4.166 1.00 4.44 C
ATOM 1715 O SER G 285 25.587 6.555 -4.382 1.00 4.82 O
ATOM 1716 N TYR G 286 27.751 5.949 -4.271 1.00 4.53 N ATOM 1717 CA TYR G 286 27.500 4.517 -4.291 1.00 4.80 C
ATOM 1718 CB TYR G 286 27.978 3.915 -5.612 1.00 4.88 C
ATOM 1719 CG TYR G 286 27.168 4.354 -6.809 1.00 5.68 C
ATOM 1720 CDl TYR G 286 27.156 5.681 -7.218 1.00 7.34 C
ATOM 1721 CE1 TYR G 286 26.429 6.081 -8.322 1.00 9.02 C
ATOM 1722 CZ TYR G 286 25.720 5.145 -9.044 1.00 9.40 C
ATOM 1723 OH TYR G 286 24.998 5.538 -10.146 1.00 10.44 O
ATOM 1724 CE2 TYR G 286 25.730 3.820 -8.668 1.00 9.38 C
ATOM 1725 CD2 TYR G 286 26.444 3.433 -7.553 1.00 7.39 C
ATOM 1726 C TYR G 286 28.208 3.845 -3.124 1.00 4.76 C
ATOM 1727 O TYR G 286 29.130 4.411 -2.541 1.00 5.25 O
ATOM 1728 N SER G 287 27.765 2.642 -2.779 1.00 4.52 N
ATOM 1729 CA SER G 287 28.528 1.786 -1.884 1.00 4.45 C
ATOM 1730 CB SER G 287 27.888 1.743 -0.496 1.00 4.57 C
ATOM 1731 OG SER G 287 28.421 0.681 0.275 1.00 4.38 O
ATOM 1732 C SER G 287 28.670 0.381 -2.454 1.00 4.61 C
ATOM 1733 O SER G 287 27.683 -0.253 -2.820 1.00 4.40 O
ATOM 1734 N ILE G 288 29.914 -0.002 -2.717 1.00 5.11 N
ATOM 1735 CA ILE G 288 30.227 -1.318 -3.258 1.00 5.81 C
ATOM 1736 CB ILE G 288 31.376 -1.250 -4.288 1.00 5.52 C
ATOM 1737 CGI ILE G 288 31.377 0.095 -5.021 1.00 5.47 C
ATOM 1738 CDl ILE G 288 31.007 0.002 -6.487 1.00 6.23 C
ATOM 1739 CG2 ILE G 288 31.298 -2.421 -5.256 1.00 6.22 C
ATOM 1740 C ILE G 288 30.664 -2.245 -2.138 1.00 6.71 C
ATOM 1741 O ILE G 288 31.615 -1.948 -1.414 1.00 7.30 O
ATOM 1742 N MET G 289 30.085 -3.438 -2.118 1.00 7.71 N
ATOM 1743 CA MET G 289 30.585 -4.515 -1.277 1.00 8.57 C
ATOM 1744 CB MET G 289 29.605 -5.692 -1.306 1.00 8.71 C
ATOM 1745 CG MET G 289 29.648 -6.584 -0.077 1.00 9.70 C
ATOM 1746 SD MET G 289 28.615 -8.046 -0.280 1.00 12.59 S
ATOM 1747 CE MET G 289 29.227 -8.678 -1.839 1.00 12.41 C
ATOM 1748 C MET G 289 31.975 -4.963 -1.736 1.00 9.12 C
ATOM 1749 O MET G 289 32.231 -5.086 -2.935 1.00 9.31 O
ATOM 1750 N SER G 290 32.891 -5.122 -0.784 1.00 9.80 N
ATOM 1751 CA SER G 290 34.272 -5.469 -1.098 1.00 10.49 C
ATOM 1752 CB SER G 290 35.242 -4.513 -0.401 1.00 10.64 C
ATOM 1753 OG SER G 290 36.498 -4.486 -1.058 1.00 11.99 O
ATOM 1754 C SER G 290 34.592 -6.918 -0.742 1.00 10.75 C
ATOM 1755 O SER G 290 34.631 -7.778 -1.621 1.00 10.89 O
ATOM 1756 N ILE G 291 34.760 -7.206 0.544 1.00 11.04 N
ATOM 1757 CA ILE G 291 34.884 -8.596 0.965 1.00 11.41 C
ATOM 1758 CB ILE G 291 36.329 -9.120 0.900 1.00 11.80 C
ATOM 1759 CGI ILE G 291 37.332 -7.977 1.061 1.00 11.81 C
ATOM 1760 CDl ILE G 291 38.227 -8.113 2.277 1.00 11.76 C
ATOM 1761 CG2 ILE G 291 36.561 -9.846 -0.416 1.00 12.39 C
ATOM 1762 C ILE G 291 34.214 -8.982 2.277 1.00 11.13 C
ATOM 1763 O ILE G 291 34.299 -8.268 3.277 1.00 10.55 O
ATOM 1764 N ILE G 292 33.536 -10.124 2.246 1.00 11.36 N
ATOM 1765 CA ILE G 292 32.802 -10.620 3.398 1.00 11.82 C
ATOM 1766 CB ILE G 292 31.359 -11.016 3.029 1.00 11.86 C
ATOM 1767 CGI ILE G 292 31.087 -10.734 1.550 1.00 13.42 C
ATOM 1768 CDl ILE G 292 31.289 -9.282 1.158 1.00 15.86 C
ATOM 1769 CG2 ILE G 292 30.358 -10.287 3.923 1.00 10.85 C
ATOM 1770 C ILE G 292 33.505 -11.826 3.992 1.00 11.72 C
ATOM 1771 O ILE G 292 33.683 -12.849 3.330 1.00 11.28 O
ATOM 1772 N LYS G 293 33.946 -11.679 5.234 1.00 12.11 N
ATOM 1773 CA LYS G 293 34.275 -12.823 6.058 1.00 12.92 C
ATOM 1774 CB LYS G 293 35.715 -12.720 6.553 1.00 13.15 C
ATOM 1775 CG LYS G 293 36.674 -12.179 5.512 1.00 14.17 C
ATOM 1776 CD LYS G 293 38.000 -12.910 5.561 1.00 15.37 C ATOM 1777 CE LYS G 293 38.720 -12.826 4.229 1.00 16.68 C
ATOM 1778 NZ LYS G 293 39.984 -13.607 4.242 1.00 18.18 N
ATOM 1779 C LYS G 293 33.310 -12.923 7.232 1.00 13.32 C
ATOM 1780 O LYS G 293 32.633 -11.952 7.578 1.00 13.17 O
ATOM 1781 N GLU G 294 33.140 -14.141 7.735 1.00 14.07 N
ATOM 1782 CA GLU G 294 32.217 -14.398 8.831 1.00 15.07 C
ATOM 1783 CB GLU G 294 32.474 -15.786 9.425 1.00 15.94 C
ATOM 1784 CG GLU G 294 32.183 -16.935 8.471 1.00 19.87 C
ATOM 1785 CD GLU G 294 32.165 -18.282 9.169 1.00 23.88 C
ATOM 1786 OE1 GLU G 294 31.348 -18.465 10.097 1.00 23.75 O
ATOM 1787 OE2 GLU G 294 32.950 -19.168 8.766 1.00 25.81 O
ATOM 1788 C GLU G 294 32.301 -13.320 9.917 1.00 14.40 C
ATOM 1789 O GLU G 294 31.281 -12.936 10.491 1.00 14.33 O
ATOM 1790 N GLU G 295 33.502 -12.779 10.132 1.00 13.97 N
ATOM 1791 CA GLU G 295 33.765 -11.861 11.251 1.00 13.84 C
ATOM 1792 CB GLU G 295 34.681 -12.508 12.299 1.00 14.67 C
ATOM 1793 CG GLU G 295 35.496 -13.688 11.794 1.00 17.56 C
ATOM 1794 CD GLU G 295 36.393 -13.328 10.626 1.00 21.41 C
ATOM 1795 OE1 GLU G 295 36.085 -13.752 9.493 1.00 22.35 O
ATOM 1796 OE2 GLU G 295 37.472 -12.745 10.861 1.00 23.20 O
ATOM 1797 C GLU G 295 34.340 -10.502 10.827 1.00 12.77 C
ATOM 1798 O GLU G 295 34.771 -9.712 11.670 1.00 12.58 O
ATOM 1799 N VAL G 296 34.389 -10.256 9.522 1.00 11.72 N
ATOM 1800 CA VAL G 296 34.634 -8.911 9.011 1.00 10.65 C
ATOM 1801 CB VAL G 296 36.143 -8.604 8.894 1.00 10.47 C
ATOM 1802 CGI VAL G 296 36.369 -7.112 8.687 1.00 9.77 C
ATOM 1803 CG2 VAL G 296 36.879 -9.090 10.133 1.00 11.31 C
ATOM 1804 C VAL G 296 33.949 -8.664 7.669 1.00 10.26 C
ATOM 1805 O VAL G 296 33.931 -9.530 6.793 1.00 10.09 O
ATOM 1806 N LEU G 297 33.379 -7.473 7.525 1.00 9.77 N
ATOM 1807 CA LEU G 297 32.842 -7.027 6.250 1.00 8.97 C
ATOM 1808 CB LEU G 297 31.332 -6.796 6.367 1.00 8.64 C
ATOM 1809 CG LEU G 297 30.643 -6.020 5.243 1.00 9.01 C
ATOM 1810 CD1 LEU G 297 30.733 -6.773 3.927 1.00 9.79 C
ATOM 1811 CD2 LEU G 297 29.194 -5.752 5.606 1.00 9.43 C
ATOM 1812 C LEU G 297 33.544 -5.745 5.821 1.00 8.34 C
ATOM 1813 O LEU G 297 33.645 -4.793 6.595 1.00 8.64 O
ATOM 1814 N ALA G 298 34.131 -5.767 4.631 1.00 7.21 N
ATOM 1815 CA ALA G 298 34.751 -4.573 4.079 1.00 6.33 C
ATOM 1816 CB ALA G 298 36.231 -4.800 3.860 1.00 6.68 C
ATOM 1817 C ALA G 298 34.074 -4.177 2.778 1.00 5.85 C
ATOM 1818 O ALA G 298 33.727 -5.033 1.965 1.00 5.96 O
ATOM 1819 N TY G 299 33.820 -2.883 2.620 1.00 5.28 N
ATOM 1820 CA TYR G 299 33.178 -2.376 1.417 1.00 4.63 C
ATOM 1821 CB TYR G 299 31.660 -2.340 1.595 1.00 4.36 C
ATOM 1822 CG TYR G 299 31.204 -1.517 2.776 1.00 4.34 C
ATOM 1823 CD1 TYR G 299 30.967 -0.156 2.648 1.00 4.48 C
ATOM 1824 CE1 TYR G 299 30.505 0.592 3.717 1.00 4.55 C
ATOM 1825 CZ TYR G 299 30.292 -0.019 4.937 1.00 3.72 C
ATOM 1826 OH TYR G 299 29.847 0.720 6.009 1.00 2.38 O
ATOM 1827 CE2 TYR G 299 30.540 -1.366 5.092 1.00 4.13 C
ATOM 1828 CD2 TYR G 299 31.007 -2.102 4.020 1.00 4.38 C
ATOM 1829 C TYR G 299 33.692 -0.988 1.063 1.00 4.32 C
ATOM 1830 O TYR G 299 34.067 -0.214 1.944 1.00 4.67 O
ATOM 1831 N VAL G 300 33.609 -0.641 -0.217 1.00 3.87 N
ATOM 1832 CA VAL G 300 34.121 0.636 -0.696 1.00 3.57 C
ATOM 1833 CB VAL G 300 34.892 0.481 -2.020 1.00 3.52 C
ATOM 1834 CGI VAL G 300 35.278 1.843 -2.576 1.00 3.44 C
ATOM 1835 CG2 VAL G 300 36.127 -0.374 -1.808 1.00 3.90 C
ATOM 1836 C VAL G 300 32.999 1.654 -0.861 1.00 3.53 C ATOM 1837 O VAL G 300 31.959 1.360 -1.451 1.00 3.68 O
ATOM 1838 N VAL G 301 33.163 2.795 -0.205 1.00 3.41 N
ATOM 1839 CA VAL G 301 32.321 3.950 -0.451 1.00 3.36 C
ATOM 1840 CB VAL G 301 32.264 4.847 0.789 1.00 3.24 C
ATOM 1841 CGI VAL G 301 31.738 6.229 0.428 1.00 3.76 C
ATOM 1842 CG2 VAL G 301 31.431 4.190 1.884 1.00 3.10 C
ATOM 1843 C VAL G 301 32.854 4.766 -1.619 1.00 3.48 C
ATOM 1844 O VAL G 301 34.065 4.911 -1.786 1.00 3.92 O
ATOM 1845 N GLN G 302 31.943 5.410 -2.339 1.00 3.21 N
ATOM 1846 CA GLN G 302 32.285 6.084 -3.578 1.00 3.01 C
ATOM 1847 CB GLN G 302 31.901 5.213 -4.775 1.00 3.24 C
ATOM 1848 CG GLN G 302 31.990 5.924 -6.113 1.00 5.21 C
ATOM 1849 CD GLN G 302 32.153 4.963 -7.271 1.00 7.54 C
ATOM 1850 OE1 GLN G 302 32.555 3.814 -7.086 1.00 7.28 O
ATOM 1851 NE2 GLN G 302 31.793 5.412 -8.467 1.00 9.27 N
ATOM 1852 C GLN G 302 31.571 7.424 -3.652 1.00 2.42 C
ATOM 1853 O GLN G 302 30.344 7.479 -3.737 1.00 2.40 O
ATOM 1854 N LEU G 303 32.323 8.492 -3.426 1.00 2.00 N
ATOM 1855 CA LEU G 303 31.729 9.802 -3.232 1.00 2.00 C
ATOM 1856 CB LEU G 303 32.303 10.471 -1.979 1.00 2.00 C
ATOM 1857 CG LEU G 303 32.332 9.619 -0.706 1.00 2.00 C
ATOM 1858 CD1 LEU G 303 32.849 10.428 0.474 1.00 2.00 C
ATOM 1859 CD2 LEU G 303 30.960 9.033 -0.400 1.00 2.00 C
ATOM 1860 C LEU G 303 31.955 10.674 -4.460 1.00 2.00 C
ATOM 1861 O LEU G 303 32.835 10.391 -5.273 1.00 2.45 O
ATOM 1862 N PRO G 304 31.136 11.723 -4.614 1.00 2.00 N
ATOM 1863 CA PRO G 304 31.230 12.520 -5.827 1.00 2.07 C
ATOM 1864 CB PRO G 304 29.999 13.432 -5.754 1.00 2.00 C
ATOM 1865 CG PRO G 304 29.497 13.323 -4.348 1.00 2.00 C
ATOM 1866 CD PRO G 304 29.880 11.966 -3.888 1.00 2.06 C
ATOM 1867 C PRO G 304 32.513 13.340 -5.854 1.00 2.11 C
ATOM 1868 O PRO G 304 32.814 14.030 -4.878 1.00 2.13 O
ATOM 1869 N ALA G 305 33.407 12.935 -6.752 1.00 30.00 N
ATOM 1870 CA ALA G 305 33.971 13.839 -7.760 1.00 30.00 C
ATOM 1871 CB ALA G 305 35.427 13.480 -8.043 1.00 30.00 C
ATOM 1872 C ALA G 305 33.151 13.838 -9.059 1.00 30.00 C
ATOM 1873 O ALA G 305 32.743 12.775 -9.530 1.00 30.00 O
ATOM 1874 N TYR G 306 32.752 15.032 -9.522 1.00 13.49 N
ATOM 1875 CA TYR G 306 31.656 15.131 -10.505 1.00 13.70 C
ATOM 1876 CB TYR G 306 30.892 16.462 -10.539 1.00 13.93 C
ATOM 1877 CG TYR G 306 31.430 17.687 -9.879 1.00 14.08 C
ATOM 1878 CD 1 TYR G 306 32.339 18.519 -10.551 1.00 14.59 C
ATOM 1879 CE1 TYR G 306 32.383 19.885 -10.286 1.00 14.82 C
ATOM 1880 CZ TYR G 306 31.470 20.425 -9.404 1.00 14.52 C
ATOM 1881 OH TYR G 306 31.626 21.709 -8.943 1.00 13.02 O
ATOM 1882 CE2 TYR G 306 30.465 19.645 -8.899 1.00 15.22 C
ATOM 1883 CD2 TYR G 306 30.596 18.296 -8.957 1.00 14.61 C
ATOM 1884 C TYR G 306 32.048 14.998 -11.938 1.00 13.68 C
ATOM 1885 O TYR G 306 33.051 14.374 -12.273 1.00 13.95 O
ATOM 1886 N GLY G 307 31.521 16.002 -12.645 1.00 13.54 N
ATOM 1887 CA GLY G 307 31.871 16.332 -14.033 1.00 13.37 C
ATOM 1888 C GLY G 307 30.772 16.073 -15.065 1.00 13.47 C
ATOM 1889 O GLY G 307 30.263 14.955 -15.138 1.00 13.90 O
ATOM 1890 N VAL G 308 30.591 16.991 -16.021 1.00 13.31 N
ATOM 1891 CA VAL G 308 29.883 16.654 -17.276 1.00 13.30 C
ATOM 1892 CB VAL G 308 28.555 15.924 -16.985 1.00 13.03 C
ATOM 1893 CGI VAL G 308 28.183 15.008 -18.138 1.00 13.62 C
ATOM 1894 CG2 VAL G 308 28.619 15.178 -15.665 1.00 12.86 C
ATOM 1895 C VAL G 308 29.425 17.870 -18.046 1.00 13.58 C
ATOM 1896 O VAL G 308 30.236 18.677 -18.508 1.00 13.71 O ATOM 1897 N ILE G 309 28.221 18.219 -17.643 1.00 4.08 N
ATOM 1898 CA ILE G 309 28.140 19.052 -16.487 1.00 4.84 C
ATOM 1899 CB ILE G 309 29.493 19.031 -15.728 1.00 4.89 C
ATOM 1900 CGI ILE G 309 29.924 17.598 -15.412 1.00 5.85 C
ATOM 1901 CD1 ILE G 309 29.235 17.007 -14.197 1.00 8.12 C
ATOM 1902 CG2 ILE G 309 29.423 19.879 -14.473 1.00 4.44 C
ATOM 1903 C ILE G 309 28.075 20.346 -17.222 1.00 5.23 C
ATOM 1904 O ILE G 309 28.803 20.526 -18.199 1.00 5.92 O
ATOM 1905 N ASP G 310 26.984 21.057 -17.020 1.00 5.33 N
ATOM 1906 CA ASP G 310 26.985 22.446 -17.403 1.00 5.83 C
ATOM 1907 CB ASP G 310 28.432 22.938 -17.554 1.00 6.21 C
ATOM 1908 CG ASP G 310 29.280 22.660 -16.321 1.00 7.19 C
ATOM 1909 OD1 ASP G 310 30.432 22.200 -16.480 1.00 7.74 O
ATOM 1910 OD2 ASP G 310 28.844 23.021 -15.209 1.00 7.58 O
ATOM 1911 C ASP G 310 26.233 22.676 -18.712 1.00 6.02 C
ATOM 1912 O ASP G 310 26.323 23.760 -19.287 1.00 6.05 O
ATOM 1913 N TH G 311 25.448 21.696 -19.157 1.00 6.24 N
ATOM 1914 CA THR G 311 24.352 21.982 -20.088 1.00 6.14 C
ATOM 1915 CB THR G 311 23.883 20.720 -20.852 1.00 5.69 C
ATOM 1916 OG1 THR G 311 24.925 19.737 -20.850 1.00 5.34 O
ATOM 1917 CG2 THR G 311 23.526 21.069 -22.291 1.00 7.10 C
ATOM 1918 C THR G 311 23.160 22.578 -19.339 1.00 6.78 C
ATOM 1919 O THR G 311 22.863 22.163 -18.218 1.00 7.33 O
ATOM 1920 N PRO G 312 22.414 23.483 -19.992 1.00 7.00 N
ATOM 1921 CA PRO G 312 21.205 23.982 -19.341 1.00 7.23 C
ATOM 1922 CB PRO G 312 20.748 25.113 -20.267 1.00 7.00 C
ATOM 1923 CG PRO G 312 21.341 24.786 -21.593 1.00 6.59 C
ATOM 1924 CD PRO G 312 22.649 24.119 -21.300 1.00 6.99 C
ATOM 1925 C PRO G 312 20.138 22.895 -19.263 1.00 7.69 C
ATOM 1926 O PRO G 312 19.973 22.130 -20.213 1.00 7.55 O
ATOM 1927 N CYS G 313 19.469 22.781 -18.120 1.00 8.10 N
ATOM 1928 CA CYS G 313 18.164 22.128 -18.088 1.00 8.54 C
ATOM 1929 CB CYS G 313 18.165 20.883 -17.192 1.00 8.77 C
ATOM 1930 SG CYS G 313 19.762 20.065 -16.969 1.00 10.74 S
ATOM 1931 C CYS G 313 17.029 23.057 -17.686 1.00 8.19 C
ATOM 1932 O CYS G 313 17.246 24.212 -17.319 1.00 8.07 O
ATOM 1933 N TRP G 314 15.832 22.485 -17.634 1.00 7.93 N
ATOM 1934 CA TRP G 314 14.663 23.177 -17.125 1.00 7.80 C
ATOM 1935 CB TRP G 314 14.110 24.131 -18.184 1.00 8.13 C
ATOM 1936 CG TRP G 314 13.856 23.474 -19.505 1.00 9.09 C
ATOM 1937 CD1 TRP G 314 12.657 23.036 -19.985 1.00 10.26 C
ATOM 1938 NE1 TRP G 314 12.807 22.540 -21.257 1.00 10.86 N
ATOM 1939 CE2 TRP G 314 14.121 22.661 -21.628 1.00 10.68 C
ATOM 1940 CD2 TRP G 314 14.813 23.243 -20.547 1.00 10.49 C
ATOM 1941 CE3 TRP G 314 16.185 23.483 -20.675 1.00 11.67 C
ATOM 1942 CZ3 TRP G 314 16.814 23.119 -21.850 1.00 12.98 C
ATOM 1943 CH2 TRP G 314 16.104 22.513 -22.894 1.00 12.74 C
ATOM 1944 CZ2 TRP G 314 14.758 22.286 -22.807 1.00 11.73 C
ATOM 1945 C TRP G 314 13.603 22.153 -16.742 1.00 7.34 C
ATOM 1946 O TRP G 314 13.578 21.044 -17.275 1.00 7.47 O
ATOM 1947 N LYS G 315 12.783 22.500 -15.757 1.00 6.75 N
ATOM 1948 CA LYS G 315 11.667 21.654 -15.363 1.00 6.37 C
ATOM 1949 CB LYS G 315 11.631 21.475 -13.844 1.00 6.38 C
ATOM 1950 CG LYS G 315 10.746 20.331 -13.374 1.00 6.55 C
ATOM 1951 CD LYS G 315 10.695 20.252 -11.854 1.00 8.01 C
ATOM 1952 CE LYS G 315 9.848 19.077 -11.383 1.00 8.78 C
ATOM 1953 NZ LYS G 315 9.177 19.368 -10.085 1.00 10.21 N
ATOM 1954 C LYS G 315 10.348 22.231 -15.855 1.00 6.32 C
ATOM 1955 O LYS G 315 10.123 23.441 -15.798 1.00 6.21 O
ATOM 1956 N LEU G 316 9.529 21.370 -16.443 1.00 6.58 N ATOM 1957 CA LEU G 316 8.273 21.796 -17.027 1.00 7.02 C
ATOM 1958 CB LEU G 316 8.140 21.253 -18.448 1.00 6.64 C
ATOM 1959 CG LEU G 316 6.756 21.379 -19.086 1.00 6.21 C
ATOM 1960 CD1 LEU G 316 6.358 22.841 -19.221 1.00 5.94 C
ATOM 1961 CD2 LEU G 316 6.730 20.687 -20.439 1.00 6.57 C
ATOM 1962 C LEU G 316 7.116 21.308 -16.172 1.00 7.77 C
ATOM 1963 O LEU G 316 6.942 20.105 -15.976 1.00 8.47 O
ATOM 1964 N HIS G 317 6.363 22.247 -15.613 1.00 8.05 N
ATOM 1965 CA HIS G 317 5.073 21.923 -15.031 1.00 8.21 C
ATOM 1966 CB HIS G 317 4.956 22.485 -13.614 1.00 9.04 C
ATOM 1967 CG HIS G 317 6.260 22.565 -12.886 1.00 11.41 C
ATOM 1968 ND1 HIS G 317 6.606 21.691 -11.877 1.00 13.62 N
ATOM 1969 CE1 HIS G 317 7.781 22.035 -11.383 1.00 14.91 C
ATOM 1970 NE2 HIS G 317 8.208 23.105 -12.029 1.00 14.25 N
ATOM 1971 CD2 HIS G 317 7.271 23.462 -12.969 1.00 12.67 C
ATOM 1972 C HIS G 317 3.943 22.453 -15.894 1.00 7.39 C
ATOM 1973 O HIS G 317 4.132 23.381 -16.680 1.00 7.23 O
ATOM 1974 N TH G 318 2.736 22.006 -15.580 1.00 7.11 N
ATOM 1975 CA THR G 318 1.704 21.826 -16.583 1.00 6.56 C
ATOM 1976 CB THR G 318 1.869 20.474 -17.309 1.00 6.28 C
ATOM 1977 OG1 TH G 318 2.413 20.694 -18.616 1.00 6.33 O
ATOM 1978 CG2 THR G 318 0.534 19.761 -17.435 1.00 6.52 C
ATOM 1979 C THR G 318 0.349 21.865 -15.893 1.00 6.58 C
ATOM 1980 O THR G 318 0.104 21.105 -14.958 1.00 6.67 O
ATOM 1981 N SER G 319 -0.501 22.802 -16.301 1.00 6.81 N
ATOM 1982 CA SER G 319 -1.840 22.911 -15.730 1.00 7.31 C
ATOM 1983 CB SER G 319 -1.929 24.106 -14.779 1.00 7.14 C
ATOM 1984 OG SER G 319 -3.255 24.292 -14.314 1.00 6.84 O
ATOM 1985 C SER G 319 -2.922 23.006 -16.800 1.00 7.93 C
ATOM 1986 O SER G 319 -2.717 23.624 -17.845 1.00 8.65 O
ATOM 1987 N PRO G 320 -4.104 22.440 -16.514 1.00 8.08 N
ATOM 1988 CA PRO G 320 -5.172 22.399 -17.500 1.00 8.34 C
ATOM 1989 CB PRO G 320 -6.336 21.738 -16.743 1.00 7.99 C
ATOM 1990 CG PRO G 320 -5.908 21.662 -15.304 1.00 8.01 C
ATOM 1991 CD PRO G 320 -4.422 21.635 -15.324 1.00 8.10 C
ATOM 1992 C PRO G 320 -5.564 23.793 -17.984 1.00 9.03 C
ATOM 1993 O PRO G 320 -5.261 24.788 -17.325 1.00 8.74 O
ATOM 1994 N LEU G 321 -6.134 23.854 -19.184 1.00 10.31 N
ATOM 1995 CA LEU G 321 -6.366 25.113 -19.885 1.00 11.63 C
ATOM 1996 CB LEU G 321 -5.207 25.402 -20.848 1.00 11.31 C
ATOM 1997 CG LEU G 321 -4.949 26.848 -21.291 1.00 10.97 C
ATOM 1998 CD1 LEU G 321 -4.174 26.884 -22.600 1.00 10.04 C
ATOM 1999 CD2 LEU G 321 -6.241 27.639 -21.416 1.00 10.69 C
ATOM 2000 C LEU G 321 -7.683 25.027 -20.662 1.00 12.92 C
ATOM 2001 O LEU G 321 -7.890 24.095 -21.439 1.00 13.29 O
ATOM 2002 N CYS G 322 -8.593 25.964 -20.400 1.00 13.39 N
ATOM 2003 CA CYS G 322 -9.923 25.955 -21.017 1.00 14.16 C
ATOM 2004 CB CYS G 322 -10.994 25.588 -19.990 1.00 13.72 C
ATOM 2005 SG CYS G 322 -10.587 24.180 -18.943 1.00 13.42 S
ATOM 2006 C CYS G 322 -10.274 27.299 -21.650 1.00 15.46 C
ATOM 2007 O CYS G 322 -10.048 28.352 -21.054 1.00 15.94 O
ATOM 2008 N THR G 323 -10.985 27.241 -22.773 1.00 16.70 N
ATOM 2009 CA THR G 323 -11.694 28.395 -23.326 1.00 17.84 C
ATOM 2010 CB THR G 323 -12.389 28.017 -24.647 1.00 17.50 C
ATOM 2011 OG1 THR G 323 -12.703 26.618 -24.638 1.00 15.70 O
ATOM 2012 CG2 THR G 323 -11.486 28.322 -25.831 1.00 18.05 C
ATOM 2013 C THR G 323 -12.756 28.915 -22.359 1.00 19.54 C
ATOM 2014 O THR G 323 -13.178 28.188 -21.461 1.00 19.84 O
ATOM 2015 N THR G 324 -13.354 30.061 -22.684 1.00 21.17 N
ATOM 2016 CA THR G 324 -14.592 30.460 -22.017 1.00 22.89 C ATOM 2017 CB TH G 324 -14.343 31.388 -20.821 1.00 22.69 C
ATOM 2018 OG1 THR G 324 -12.937 31.469 -20.560 1.00 22.10 O
ATOM 2019 CG2 THR G 324 -15.061 30.857 -19.587 1.00 22.03 C
ATOM 2020 C THR G 324 -15.712 31.033 -22.885 1.00 24.39 C
ATOM 2021 O THR G 324 -16.838 31.194 -22.414 1.00 24.53 O
ATOM 2022 N ASN G 325 -15.427 31.299 -24.155 1.00 25.72 N
ATOM 2023 CA ASN G 325 -16.490 31.473 -25.144 1.00 27.01 C
ATOM 2024 CB ASN G 325 -16.986 32.922 -25.170 1.00 27.37 C
ATOM 2025 CG ASN G 325 -18.079 33.184 -24.148 1.00 28.46 C
ATOM 2026 OD1 ASN G 325 -19.267 33.164 -24.471 1.00 30.37 O
ATOM 2027 ND2 ASN G 325 -17.678 33.444 -22.909 1.00 28.78 N
ATOM 2028 C ASN G 325 -16.075 31.032 -26.543 1.00 27.36 C
ATOM 2029 O ASN G 325 -14.887 30.902 -26.837 1.00 27.94 O
ATOM 2030 N SER G 330 -15.165 27.730 -23.322 1.00 35.76 N
ATOM 2031 CA SER G 330 -16.301 26.817 -23.281 1.00 35.01 C
ATOM 2032 CB SER G 330 -17.459 27.366 -24.117 1.00 35.47 C
ATOM 2033 OG SER G 330 -17.137 27.368 -25.497 1.00 33.31 O
ATOM 2034 C SER G 330 -15.906 25.431 -23.779 1.00 34.35 C
ATOM 2035 O SER G 330 -15.111 25.299 -24.709 1.00 34.33 O
ATOM 2036 N ASN G 331 -16.430 24.399 -23.128 1.00 32.48 N
ATOM 2037 CA ASN G 331 -16.609 23.102 -23.770 1.00 30.72 C
ATOM 2038 CB ASN G 331 -17.432 23.247 -25.060 1.00 31.31 C
ATOM 2039 CG ASN G 331 -18.924 23.445 -24.801 1.00 32.11 C
ATOM 2040 OD1 ASN G 331 -19.426 23.149 -23.716 1.00 32.54 O
ATOM 2041 ND2 ASN G 331 -19.651 23.849 -25.838 1.00 31.30 N
ATOM 2042 C ASN G 331 -15.298 22.357 -24.074 1.00 28.71 C
ATOM 2043 O ASN G 331 -15.322 21.324 -24.741 1.00 29.07 O
ATOM 2044 N ILE G 332 -14.155 22.896 -23.649 1.00 25.44 N
ATOM 2045 CA ILE G 332 -12.868 22.313 -24.053 1.00 21.83 C
ATOM 2046 CB ILE G 332 -12.546 22.613 -25.536 1.00 21.42 C
ATOM 2047 CGI ILE G 332 -11.286 21.867 -25.981 1.00 19.89 C
ATOM 2048 CD 1 ILE G 332 -11.573 20.576 -26.724 1.00 17.67 C
ATOM 2049 CG2 ILE G 332 -12.428 24.111 -25.776 1.00 20.61 C
ATOM 2050 C ILE G 332 -11.667 22.657 -23.162 1.00 20.37 C
ATOM 2051 O ILE G 332 -11.388 23.829 -22.903 1.00 19.95 O
ATOM 2052 N CYS G 333 -10.896 21.634 -22.794 1.00 18.27 N
ATOM 2053 CA CYS G 333 -9.666 21.842 -22.031 1.00 16.47 C
ATOM 2054 CB CYS G 333 -9.923 21.703 -20.529 1.00 16.14 C
ATOM 2055 SG CYS G 333 -11.374 22.595 -19.936 1.00 17.09 S
ATOM 2056 C CYS G 333 -8.480 20.967 -22.450 1.00 15.73 C
ATOM 2057 O CYS G 333 -8.652 19.820 -22.871 1.00 15.43 O
ATOM 2058 N LEU G 334 -7.298 21.425 -22.047 1.00 15.06 N
ATOM 2059 CA LEU G 334 -6.022 20.883 -22.498 1.00 13.79 C
ATOM 2060 CB LEU G 334 -5.346 21.857 -23.472 1.00 13.39 C
ATOM 2061 CG LEU G 334 -5.891 21.998 -24.895 1.00 13.93 C
ATOM 2062 CD1 LEU G 334 -4.764 22.327 -25.858 1.00 14.20 C
ATOM 2063 CD2 LEU G 334 -6.617 20.739 -25.331 1.00 14.52 C
ATOM 2064 C LEU G 334 -5.142 20.748 -21.263 1.00 13.22 C
ATOM 2065 O LEU G 334 -5.033 21.685 -20.472 1.00 13.31 O
ATOM 2066 N THR G 335 -4.417 19.640 -21.169 1.00 12.58 N
ATOM 2067 CA THR G 335 -3.277 19.561 -20.268 1.00 12.17 C
ATOM 2068 CB THR G 335 -3.612 18.748 -19.001 1.00 12.02 C
ATOM 2069 OG1 THR G 335 -5.021 18.815 -18.744 1.00 12.64 O
ATOM 2070 CG2 THR G 335 -2.858 19.295 -17.803 1.00 11.47 C
ATOM 2071 C THR G 335 -2.093 18.930 -20.986 1.00 11.97 C
ATOM 2072 O THR G 335 -2.258 17.980 -21.751 1.00 11.93 O
ATOM 2073 N ARG G 336 -0.942 19.586 -20.892 1.00 11.60 N
ATOM 2074 CA ARG G 336 0.254 19.122 -21.578 1.00 12.15 C
ATOM 2075 CB ARG G 336 1.293 20.239 -21.640 1.00 12.16 C
ATOM 2076 CG ARG G 336 2.162 20.208 -22.879 1.00 12.67 C ATOM 2077 CD A G G 336 2.261 21.590 -23.500 1.00 12.52 C
ATOM 2078 NE ARG G 336 3.341 22.374 -22.912 1.00 12.35 N
ATOM 2079 CZ ARG G 336 4.632 22.136 -23.117 1.00 12.54 C
ATOM 2080 NH1 ARG G 336 5.006 21.109 -23.867 1.00 12.38 N
ATOM 2081 NH2 ARG G 336 5.549 22.904 -22.545 1.00 12.48 N
ATOM 2082 C ARG G 336 0.841 17.907 -20.872 1.00 12.71 C
ATOM 2083 O ARG G 336 1.185 17.974 -19.693 1.00 12.62 O
ATOM 2084 N THR G 337 0.885 16.779 -21.574 1.00 13.70 N
ATOM 2085 CA THR G 337 1.284 15.514 -20.964 1.00 14.91 C
ATOM 2086 CB THR G 337 1.084 14.331 -21.931 1.00 15.27 C
ATOM 2087 OG1 THR G 337 -0.264 14.329 -22.421 1.00 16.65 O
ATOM 2088 CG2 THR G 337 1.370 13.015 -21.226 1.00 15.94 C
ATOM 2089 C THR G 337 2.744 15.546 -20.519 1.00 15.16 C
ATOM 2090 O THR G 337 3.069 15.159 -19.396 1.00 15.60 O
ATOM 2091 N ASP G 338 3.623 15.968 -21.424 1.00 15.15 N
ATOM 2092 CA ASP G 338 5.055 15.721 -21.283 1.00 15.52 C
ATOM 2093 CB ASP G 338 5.781 15.935 -22.613 1.00 16.81 C
ATOM 2094 CG ASP G 338 5.051 16.899 -23.529 1.00 20.57 C
ATOM 2095 OD1 ASP G 338 5.160 16.744 -24.763 1.00 23.00 O
ATOM 2096 OD2 ASP G 338 4.290 17.747 -23.017 1.00 22.92 O
ATOM 2097 C ASP G 338 5.674 16.595 -20.201 1.00 14.21 C
ATOM 2098 O ASP G 338 6.235 17.654 -20.486 1.00 14.00 O
ATOM 2099 N ARG G 339 5.617 16.113 -18.965 1.00 12.79 N
ATOM 2100 CA ARG G 339 6.087 16.877 -17.822 1.00 11.71 C
ATOM 2101 CB ARG G 339 5.108 16.747 -16.665 1.00 11.73 C
ATOM 2102 CG ARG G 339 3.773 17.383 -16.931 1.00 12.49 C
ATOM 2103 CD ARG G 339 3.116 17.761 -15.633 1.00 13.24 C
ATOM 2104 NE ARG G 339 1.712 17.370 -15.607 1.00 12.04 N
ATOM 2105 CZ ARG G 339 0.844 17.804 -14.703 1.00 11.74 C
ATOM 2106 NH1 ARG G 339 1.259 18.579 -13.710 1.00 13.43 N
ATOM 2107 NH2 ARG G 339 -0.427 17.428 -14.759 1.00 9.80 N
ATOM 2108 C ARG G 339 7.443 16.388 -17.365 1.00 11.16 C
ATOM 2109 O ARG G 339 7.703 15.185 -17.376 1.00 11.37 O
ATOM 2110 N GLY G 340 8.141 17.269 -16.660 1.00 10.43 N
ATOM 2111 CA GLY G 340 9.340 16.886 -15.933 1.00 9.52 C
ATOM 2112 C GLY G 340 10.559 17.608 -16.465 1.00 8.80 C
ATOM 2113 O GLY G 340 10.475 18.759 -16.903 1.00 8.56 O
ATOM 2114 N TRP G 341 11.700 16.935 -16.411 1.00 8.25 N
ATOM 2115 CA TRP G 341 12.965 17.581 -16.704 1.00 7.98 C
ATOM 2116 CB TRP G 341 14.089 16.966 -15.879 1.00 7.79 C
ATOM 2117 CG TRP G 341 14.110 17.460 -14.478 1.00 7.67 C
ATOM 2118 CD1 TRP G 341 13.519 16.869 -13.399 1.00 8.12 C
ATOM 2119 NE1 TRP G 341 13.686 17.648 -12.283 1.00 8.60 N
ATOM 2120 CE2 TRP G 341 14.304 18.815 -12.649 1.00 7.57 C
ATOM 2121 CD2 TRP G 341 14.536 18.754 -14.037 1.00 7.52 C
ATOM 2122 CE3 TRP G 341 15.176 19.830 -14.663 1.00 7.86 C
ATOM 2123 CZ3 TRP G 341 15.535 20.925 -13.898 1.00 7.14 C
ATOM 2124 CH2 TRP G 341 15.279 20.962 -12.521 1.00 6.39 C
ATOM 2125 CZ2 TRP G 341 14.663 19.919 -11.880 1.00 7.30 C
ATOM 2126 C TRP G 341 13.286 17.490 -18.180 1.00 8.26 C
ATOM 2127 O TRP G 341 13.320 16.402 -18.755 1.00 8.35 O
ATOM 2128 N TYR G 342 13.400 18.649 -18.811 1.00 8.44 N
ATOM 2129 CA TYR G 342 14.197 18.777 -20.012 1.00 8.53 C
ATOM 2130 CB TYR G 342 13.486 19.670 -21.015 1.00 8.43 C
ATOM 2131 CG TYR G 342 12.099 19.192 -21.318 1.00 9.17 C
ATOM 2132 CD1 TYR G 342 11.097 19.299 -20.363 1.00 10.32 C
ATOM 2133 CE1 TYR G 342 9.849 18.765 -20.582 1.00 10.99 C
ATOM 2134 CZ TYR G 342 9.618 18.033 -21.724 1.00 11.00 C
ATOM 2135 OH TYR G 342 8.365 17.521 -21.964 1.00 12.82 O
ATOM 2136 CE2 TYR G 342 10.626 17.838 -22.643 1.00 10.67 C ATOM 2137 CD2 TY G 342 11.871 18.365 -22.403 1.00 10.41 C
ATOM 2138 C TYR G 342 15.550 19.359 -19.680 1.00 8.64 C
ATOM 2139 O TYR G 342 15.754 19.906 -18.596 1.00 8.40 O
ATOM 2140 N CYS G 343 16.460 19.284 -20.641 1.00 8.87 N
ATOM 2141 CA CYS G 343 17.875 19.346 -20.332 1.00 9.35 C
ATOM 2142 CB CYS G 343 18.190 18.501 -19.092 1.00 9.17 C
ATOM 2143 SG CYS G 343 19.879 18.684 -18.466 1.00 11.88 S
ATOM 2144 C CYS G 343 18.722 18.920 -21.524 1.00 9.42 C
ATOM 2145 O CYS G 343 18.505 17.856 -22.103 1.00 9.96 O
ATOM 2146 N ASP G 344 19.534 19.857 -22.005 1.00 9.36 N
ATOM 2147 CA ASP G 344 20.127 19.778 -23.338 1.00 9.24 C
ATOM 2148 CB ASP G 344 20.797 21.108 -23.703 1.00 9.34 C
ATOM 2149 CG ASP G 344 19.874 22.037 -24.474 1.00 10.72 C
ATOM 2150 OD1 ASP G 344 19.475 21.677 -25.602 1.00 13.93 O
ATOM 2151 OD2 ASP G 344 19.548 23.127 -23.954 1.00 11.87 O
ATOM 2152 C ASP G 344 21.148 18.651 -23.425 1.00 9.09 C
ATOM 2153 O ASP G 344 22.100 18.605 -22.646 1.00 9.39 O
ATOM 2154 N ASN G 345 21.038 17.843 -24.474 1.00 9.13 N
ATOM 2155 CA ASN G 345 22.114 16.939 -24.849 1.00 9.52 C
ATOM 2156 CB ASN G 345 21.589 15.509 -24.978 1.00 9.61 C
ATOM 2157 CG ASN G 345 22.640 14.472 -24.643 1.00 9.21 C
ATOM 2158 OD1 ASN G 345 23.121 14.400 -23.512 1.00 6.21 O
ATOM 2159 ND2 ASN G 345 23.032 13.685 -25.638 1.00 11.05 N
ATOM 2160 C ASN G 345 22.772 17.381 -26.149 1.00 10.06 C
ATOM 2161 O ASN G 345 22.506 18.476 -26.644 1.00 11.10 O
ATOM 2162 N ALA G 346 23.644 16.539 -26.692 1.00 9.74 N
ATOM 2163 CA ALA G 346 24.410 16.904 -27.877 1.00 9.58 C
ATOM 2164 CB ALA G 346 25.241 15.723 -28.356 1.00 9.60 C
ATOM 2165 C ALA G 346 23.498 17.406 -28.994 1.00 9.66 C
ATOM 2166 O ALA G 346 22.977 16.618 -29.782 1.00 9.39 O
ATOM 2167 N GLY G 347 23.290 18.720 -29.038 1.00 10.04 N
ATOM 2168 CA GLY G 347 22.598 19.358 -30.157 1.00 10.68 C
ATOM 2169 C GLY G 347 21.105 19.098 -30.137 1.00 10.90 C
ATOM 2170 O GLY G 347 20.366 19.569 -31.002 1.00 11.46 O
ATOM 2171 N SER G 348 20.691 18.235 -29.219 1.00 10.30 N
ATOM 2172 CA SER G 348 19.301 17.838 -29.098 1.00 9.94 C
ATOM 2173 CB SER G 348 19.103 16.421 -29.639 1.00 9.88 C
ATOM 2174 OG SER G 348 19.440 16.352 -31.013 1.00 10.09 O
ATOM 2175 C SER G 348 18.950 17.883 -27.624 1.00 9.60 C
ATOM 2176 O SER G 348 19.775 18.267 -26.796 1.00 9.59 O
ATOM 2177 N VAL G 349 17.723 17.505 -27.292 1.00 9.54 N
ATOM 2178 CA VAL G 349 17.254 17.643 -25.925 1.00 9.56 C
ATOM 2179 CB VAL G 349 16.091 18.639 -25.823 1.00 9.28 C
ATOM 2180 CGI VAL G 349 15.814 18.985 -24.360 1.00 9.24 C
ATOM 2181 CG2 VAL G 349 16.391 19.892 -26.641 1.00 9.94 C
ATOM 2182 C VAL G 349 16.824 16.309 -25.341 1.00 9.59 C
ATOM 2183 O VAL G 349 16.029 15.585 -25.939 1.00 9.69 O
ATOM 2184 N SER G 350 17.288 16.029 -24.130 1.00 9.93 N
ATOM 2185 CA SER G 350 16.915 14.800 -23.451 1.00 10.44 C
ATOM 2186 CB SER G 350 18.146 14.108 -22.858 1.00 10.04 C
ATOM 2187 OG SER G 350 18.768 13.261 -23.812 1.00 8.41 O
ATOM 2188 C SER G 350 15.854 15.039 -22.381 1.00 11.45 C
ATOM 2189 O SER G 350 15.882 16.041 -21.665 1.00 11.58 O
ATOM 2190 N PHE G 351 14.893 14.126 -22.318 1.00 12.28 N
ATOM 2191 CA PHE G 351 13.722 14.291 -21.469 1.00 13.04 C
ATOM 2192 CB PHE G 351 12.468 14.485 -22.321 1.00 12.87 C
ATOM 2193 CG PHE G 351 11.192 14.388 -21.539 1.00 13.52 C
ATOM 2194 CD1 PHE G 351 11.026 15.127 -20.378 1.00 13.76 C
ATOM 2195 CE1 PHE G 351 9.857 15.044 -19.648 1.00 14.10 C
ATOM 2196 CZ PHE G 351 8.855 14.175 -20.045 1.00 14.07 C ATOM 2197 CE2 PHE G 351 9.028 13.395 -21.172 1.00 14.14 C
ATOM 2198 CD2 PHE G 351 10.202 13.489 -21.903 1.00 13.92 C
ATOM 2199 C PHE G 351 13.526 13.082 -20.563 1.00 13.84 C
ATOM 2200 O PHE G 351 13.246 11.979 -21.038 1.00 13.96 O
ATOM 2201 N PHE G 352 13.463 13.340 -19.263 1.00 14.72 N
ATOM 2202 CA PHE G 352 13.315 12.275 -18.286 1.00 15.98 C
ATOM 2203 CB PHE G 352 14.429 12.360 -17.243 1.00 15.75 C
ATOM 2204 CG PHE G 352 15.720 12.912 -17.780 1.00 15.51 C
ATOM 2205 CD1 PHE G 352 15.899 14.279 -17.924 1.00 15.05 C
ATOM 2206 CE1 PHE G 352 17.098 14.793 -18.375 1.00 14.05 C
ATOM 2207 CZ PHE G 352 18.126 13.938 -18.719 1.00 13.28 C
ATOM 2208 CE2 PHE G 352 17.948 12.570 -18.615 1.00 13.71 C
ATOM 2209 CD2 PHE G 352 16.745 12.064 -18.163 1.00 14.94 C
ATOM 2210 C PHE G 352 11.952 12.360 -17.612 1.00 17.56 C
ATOM 2211 O PHE G 352 11.591 13.401 -17.066 1.00 17.74 O
ATOM 2212 N PRO G 353 11.165 11.280 -17.705 1.00 19.05 N
ATOM 2213 CA PRO G 353 9.719 11.355 -17.537 1.00 20.40 C
ATOM 2214 CB PRO G 353 9.220 10.060 -18.189 1.00 20.26 C
ATOM 2215 CG PRO G 353 10.352 9.587 -19.046 1.00 19.71 C
ATOM 2216 CD PRO G 353 11.580 10.012 -18.325 1.00 18.97 C
ATOM 2217 C PRO G 353 9.291 11.404 -16.072 1.00 21.94 C
ATOM 2218 O PRO G 353 8.222 11.935 -15.768 1.00 22.29 O
ATOM 2219 N GLN G 354 10.105 10.851 -15.175 1.00 23.38 N
ATOM 2220 CA GLN G 354 9.731 10.792 -13.761 1.00 24.64 C
ATOM 2221 CB GLN G 354 9.107 9.440 -13.400 1.00 24.93 C
ATOM 2222 CG GLN G 354 9.407 8.322 -14.376 1.00 26.00 C
ATOM 2223 CD GLN G 354 10.859 7.909 -14.354 1.00 25.92 C
ATOM 2224 OE1 GLN G 354 11.380 7.473 -13.327 1.00 25.67 O
ATOM 2225 NE2 GLN G 354 11.521 8.030 -15.498 1.00 24.27 N
ATOM 2226 C GLN G 354 10.823 11.177 -12.759 1.00 24.85 C
ATOM 2227 O GLN G 354 12.009 10.943 -12.989 1.00 24.51 O
ATOM 2228 N ALA G 355 10.392 11.709 -11.618 1.00 25.22 N
ATOM 2229 CA ALA G 355 11.296 12.264 -10.619 1.00 25.34 C
ATOM 2230 CB ALA G 355 10.565 12.449 -9.296 1.00 25.09 C
ATOM 2231 C ALA G 355 12.531 11.390 -10.427 1.00 24.92 C
ATOM 2232 O ALA G 355 13.646 11.791 -10.766 1.00 25.23 O
ATOM 2233 N GLU G 356 12.339 10.258 -9.755 1.00 23.93 N
ATOM 2234 CA GLU G 356 13.282 9.141 -9.803 1.00 22.77 C
ATOM 2235 CB GLU G 356 12.642 7.925 -10.474 1.00 23.22 C
ATOM 2236 CG GLU G 356 11.489 7.338 -9.681 1.00 26.33 C
ATOM 2237 CD GLU G 356 11.607 7.632 -8.199 1.00 30.93 C
ATOM 2238 OE1 GLU G 356 11.148 8.711 -7.764 1.00 31.97 O
ATOM 2239 OE2 GLU G 356 12.276 6.846 -7.494 1.00 32.21 O
ATOM 2240 C GLU G 356 14.591 9.493 -10.492 1.00 21.31 C
ATOM 2241 O GLU G 356 15.656 9.462 -9.876 1.00 21.01 O
ATOM 2242 N THR G 357 14.511 9.752 -11.791 1.00 19.51 N
ATOM 2243 CA THR G 357 15.690 9.787 -12.639 1.00 17.55 C
ATOM 2244 CB THR G 357 15.305 9.928 -14.114 1.00 17.30 C
ATOM 2245 OG1 THR G 357 13.908 9.660 -14.273 1.00 17.32 O
ATOM 2246 CG2 THR G 357 16.099 8.958 -14.957 1.00 17.72 C
ATOM 2247 C THR G 357 16.596 10.949 -12.262 1.00 16.62 C
ATOM 2248 O THR G 357 17.761 10.991 -12.655 1.00 17.29 O
ATOM 2249 N CYS G 358 16.028 11.935 -11.579 1.00 14.88 N
ATOM 2250 CA CYS G 358 16.684 13.225 -11.440 1.00 13.15 C
ATOM 2251 CB CYS G 358 16.025 14.262 -12.349 1.00 13.04 C
ATOM 2252 SG CYS G 358 16.175 13.900 -14.114 1.00 14.02 S
ATOM 2253 C CYS G 358 16.711 13.714 -9.997 1.00 12.08 C
ATOM 2254 O CYS G 358 15.705 13.661 -9.289 1.00 12.15 O
ATOM 2255 N LYS G 359 17.890 14.140 -9.554 1.00 11.35 N
ATOM 2256 CA LYS G 359 18.024 14.888 -8.311 1.00 11.01 C ATOM 2257 CB LYS G 359 18.968 14.165 -7.353 1.00 11.16 C
ATOM 2258 CG LYS G 359 19.450 12.824 -7.857 1.00 13.28 C
ATOM 2259 CD LYS G 359 19.029 11.720 -6.912 1.00 16.11 C
ATOM 2260 CE LYS G 359 19.561 10.378 -7.366 1.00 17.91 C
ATOM 2261 NZ LYS G 359 18.972 9.264 -6.575 1.00 20.99 N
ATOM 2262 C LYS G 359 18.561 16.282 -8.584 1.00 10.46 C
ATOM 2263 O LYS G 359 19.145 16.533 -9.637 1.00 10.70 O
ATOM 2264 N VAL G 360 18.526 17.128 -7.564 1.00 9.99 N
ATOM 2265 CA VAL G 360 18.797 18.538 -7.763 1.00 9.84 C
ATOM 2266 CB VAL G 360 17.573 19.270 -8.346 1.00 9.42 C
ATOM 2267 CGI VAL G 360 16.360 19.095 -7.442 1.00 10.07 C
ATOM 2268 CG2 VAL G 360 17.886 20.740 -8.572 1.00 9.56 C
ATOM 2269 C VAL G 360 19.259 19.211 -6.478 1.00 9.98 C
ATOM 2270 O VAL G 360 18.707 18.970 -5.405 1.00 9.96 O
ATOM 2271 N GLN G 361 20.372 19.931 -6.578 1.00 10.39 N
ATOM 2272 CA GLN G 361 20.979 20.583 -5.427 1.00 11.53 C
ATOM 2273 CB GLN G 361 22.220 19.809 -4.971 1.00 12.03 C
ATOM 2274 CG GLN G 361 22.907 20.381 -3.737 1.00 16.44 C
ATOM 2275 CD GLN G 361 23.241 19.314 -2.714 1.00 25.16 C
ATOM 2276 OE1 GLN G 361 24.398 18.921 -2.564 1.00 29.01 O
ATOM 2277 NE2 GLN G 361 22.220 18.812 -2.029 1.00 27.20 N
ATOM 2278 C GLN G 361 21.373 22.005 -5.794 1.00 11.15 C
ATOM 2279 O GLN G 361 22.354 22.221 -6.506 1.00 11.80 O
ATOM 2280 N SER G 362 20.611 22.976 -5.308 1.00 10.90 N
ATOM 2281 CA SER G 362 20.759 24.332 -5.798 1.00 10.30 C
ATOM 2282 CB SER G 362 22.208 24.792 -5.625 1.00 10.47 C
ATOM 2283 OG SER G 362 22.406 26.082 -6.179 1.00 11.17 O
ATOM 2284 C SER G 362 20.385 24.348 -7.272 1.00 9.58 C
ATOM 2285 O SER G 362 19.409 23.717 -7.677 1.00 9.48 O
ATOM 2286 N ASN G 363 21.256 24.926 -8.089 1.00 9.12 N
ATOM 2287 CA ASN G 363 21.023 24.985 -9.525 1.00 8.73 C
ATOM 2288 CB ASN G 363 21.537 26.308 -10.085 1.00 9.01 C
ATOM 2289 CG ASN G 363 23.018 26.497 -9.849 1.00 9.29 C
ATOM 2290 OD1 ASN G 363 23.681 25.636 -9.270 1.00 9.82 O
ATOM 2291 ND2 ASN G 363 23.555 27.615 -10.323 1.00 10.08 N
ATOM 2292 C ASN G 363 21.701 23.822 -10.237 1.00 8.12 C
ATOM 2293 O ASN G 363 21.961 23.881 -11.439 1.00 8.10 O
ATOM 2294 N ARG G 364 22.103 22.828 -9.453 1.00 7.20 N
ATOM 2295 CA ARG G 364 22.733 21.628 -9.984 1.00 6.82 C
ATOM 2296 CB ARG G 364 23.843 21.154 -9.044 1.00 6.91 C
ATOM 2297 CG ARG G 364 25.110 20.721 -9.754 1.00 7.92 C
ATOM 2298 CD ARG G 364 25.588 21.797 -10.709 1.00 8.20 C
ATOM 2299 NE ARG G 364 25.809 21.275 -12.053 1.00 8.70 N
ATOM 2300 CZ ARG G 364 26.690 21.777 -12.910 1.00 8.88 C
ATOM 2301 NHl ARG G 364 27.407 22.843 -12.578 1.00 8.57 N
ATOM 2302 NH2 ARG G 364 26.840 21.228 -14.107 1.00 10.59 N
ATOM 2303 C ARG G 364 21.703 20.519 -10.166 1.00 6.58 C
ATOM 2304 O ARG G 364 20.980 20.173 -9.233 1.00 6.65 O
ATOM 2305 N VAL G 365 21.719 19.897 -11.341 1.00 6.64 N
ATOM 2306 CA VAL G 365 20.802 18.805 -11.658 1.00 6.54 C
ATOM 2307 CB VAL G 365 19.823 19.208 -12.782 1.00 5.95 C
ATOM 2308 CGI VAL G 365 19.069 17.993 -13.302 1.00 5.48 C
ATOM 2309 CG2 VAL G 365 18.861 20.277 -12.291 1.00 6.22 C
ATOM 2310 C VAL G 365 21.569 17.549 -12.089 1.00 7.35 C
ATOM 2311 O VAL G 365 22.611 17.641 -12.740 1.00 8.33 O
ATOM 2312 N PHE G 366 21.009 16.380 -11.781 1.00 7.37 N
ATOM 2313 CA PHE G 366 21.654 15.097 -12.072 1.00 7.44 C
ATOM 2314 CB PHE G 366 22.371 14.567 -10.822 1.00 7.30 C
ATOM 2315 CG PHE G 366 23.464 15.468 -10.314 1.00 6.70 C
ATOM 2316 CD1 PHE G 366 23.160 16.576 -9.538 1.00 6.70 C ATOM 2317 CE1 PHE G 366 24.162 17.406 -9.068 1.00 5.94 C
ATOM 2318 CZ PHE G 366 25.487 17.053 -9.244 1.00 5.71 C
ATOM 2319 CE2 PHE G 366 25.804 15.897 -9.935 1.00 5.96 C
ATOM 2320 CD2 PHE G 366 24.793 15.094 -10.437 1.00 6.52 C
ATOM 2321 C PHE G 366 20.626 14.059 -12.546 1.00 7.45 C
ATOM 2322 O PHE G 366 19.770 13.635 -11.769 1.00 7.45 O
ATOM 2323 N CYS G 367 20.783 13.569 -13.777 1.00 8.00 N
ATOM 2324 CA CYS G 367 19.838 12.602 -14.369 1.00 8.90 C
ATOM 2325 CB CYS G 367 18.879 13.313 -15.335 1.00 9.46 C
ATOM 2326 SG CYS G 367 17.966 14.707 -14.624 1.00 10.79 S
ATOM 2327 C CYS G 367 20.563 11.445 -15.089 1.00 9.09 C
ATOM 2328 O CYS G 367 21.751 11.556 -15.396 1.00 9.24 O
ATOM 2329 N ASP G 368 19.864 10.330 -15.323 1.00 9.54 N
ATOM 2330 CA ASP G 368 20.480 9.110 -15.890 1.00 10.55 C
ATOM 2331 CB ASP G 368 20.253 7.906 -14.962 1.00 10.53 C
ATOM 2332 CG ASP G 368 21.043 6.674 -15.386 1.00 11.11 C
ATOM 2333 OD1 ASP G 368 21.241 6.475 -16.603 1.00 11.42 O
ATOM 2334 OD2 ASP G 368 21.441 5.892 -14.497 1.00 11.35 O
ATOM 2335 C ASP G 368 19.947 8.774 -17.285 1.00 11.45 C
ATOM 2336 O ASP G 368 19.035 7.958 -17.422 1.00 12.05 O
ATOM 2337 N TH G 369 20.606 9.281 -18.321 1.00 12.41 N
ATOM 2338 CA THR G 369 20.367 8.772 -19.666 1.00 13.00 C
ATOM 2339 CB THR G 369 21.685 8.338 -20.361 1.00 12.69 C
ATOM 2340 OG1 THR G 369 22.580 9.456 -20.444 1.00 11.72 O
ATOM 2341 CG2 THR G 369 21.409 7.813 -21.765 1.00 13.33 C
ATOM 2342 C THR G 369 19.406 7.585 -19.574 1.00 14.13 C
ATOM 2343 O THR G 369 18.260 7.681 -20.008 1.00 14.72 O
ATOM 2344 N MET G 370 19.790 6.577 -18.795 1.00 15.25 N
ATOM 2345 CA MET G 370 19.286 5.221 -18.993 1.00 16.60 C
ATOM 2346 CB MET G 370 19.132 4.486 -17.664 1.00 17.42 C
ATOM 2347 CG MET G 370 19.948 3.204 -17.580 1.00 20.31 C
ATOM 2348 SD MET G 370 19.542 1.991 -18.855 1.00 26.43 S
ATOM 2349 CE MET G 370 20.369 2.694 -20.281 1.00 24.07 C
ATOM 2350 C MET G 370 17.997 5.144 -19.811 1.00 16.54 C
ATOM 2351 O MET G 370 17.975 4.516 -20.870 1.00 16.74 O
ATOM 2352 N ASN G 371 16.923 5.762 -19.327 1.00 16.35 N
ATOM 2353 CA ASN G 371 15.648 5.694 -20.042 1.00 16.07 C
ATOM 2354 CB ASN G 371 14.554 5.050 -19.184 1.00 16.41 C
ATOM 2355 CG ASN G 371 14.652 3.531 -19.153 1.00 16.71 C
ATOM 2356 OD1 ASN G 371 14.117 2.843 -20.025 1.00 15.75 O
ATOM 2357 ND2 ASN G 371 15.228 3.003 -18.080 1.00 17.76 N
ATOM 2358 C ASN G 371 15.160 7.004 -20.661 1.00 15.55 C
ATOM 2359 O ASN G 371 14.132 7.023 -21.334 1.00 15.84 O
ATOM 2360 N SER G 372 16.006 8.030 -20.612 1.00 14.76 N
ATOM 2361 CA SER G 372 15.784 9.270 -21.364 1.00 13.91 C
ATOM 2362 CB SER G 372 17.101 10.025 -21.561 1.00 14.04 C
ATOM 2363 OG SER G 372 17.984 9.303 -22.405 1.00 15.09 O
ATOM 2364 C SER G 372 15.111 9.064 -22.717 1.00 13.07 C
ATOM 2365 O SER G 372 15.417 8.111 -23.437 1.00 13.02 O
ATOM 2366 N LEU G 373 14.347 10.072 -23.130 1.00 12.23 N
ATOM 2367 CA LEU G 373 13.882 10.192 -24.508 1.00 11.45 C
ATOM 2368 CB LEU G 373 12.358 10.365 -24.534 1.00 11.43 C
ATOM 2369 CG LEU G 373 11.464 9.123 -24.683 1.00 11.04 C
ATOM 2370 CD 1 LEU G 373 11.965 7.948 -23.852 1.00 11.76 C
ATOM 2371 CD2 LEU G 373 10.020 9.434 -24.330 1.00 10.49 C
ATOM 2372 C LEU G 373 14.550 11.392 -25.176 1.00 11.17 C
ATOM 2373 O LEU G 373 14.658 12.460 -24.574 1.00 11.27 O
ATOM 2374 N THR G 374 15.011 11.208 -26.411 1.00 10.70 N
ATOM 2375 CA THR G 374 15.791 12.235 -27.102 1.00 10.23 C
ATOM 2376 CB THR G 374 16.998 11.634 -27.863 1.00 10.24 C ATOM 2377 OG1 TH G 374 17.406 10.410 -27.239 1.00 11.25 O
ATOM 2378 CG2 THR G 374 18.168 12.612 -27.872 1.00 10.52 C
ATOM 2379 C THR G 374 14.934 13.032 -28.079 1.00 9.54 C
ATOM 2380 O THR G 374 14.316 12.468 -28.983 1.00 9.70 O
ATOM 2381 N LEU G 375 14.965 14.352 -27.935 1.00 8.83 N
ATOM 2382 CA LEU G 375 14.013 15.221 -28.611 1.00 7.83 C
ATOM 2383 CB LEU G 375 12.949 15.719 -27.631 1.00 7.38 C
ATOM 2384 CG LEU G 375 12.160 14.689 -26.824 1.00 5.06 C
ATOM 2385 CD1 LEU G 375 11.352 15.385 -25.741 1.00 2.41 C
ATOM 2386 CD2 LEU G 375 11.246 13.885 -27.734 1.00 4.31 C
ATOM 2387 C LEU G 375 14.728 16.416 -29.222 1.00 7.79 C
ATOM 2388 O LEU G 375 15.743 16.872 -28.696 1.00 7.92 O
ATOM 2389 N PRO G 376 14.102 17.026 -30.234 1.00 7.51 N
ATOM 2390 CA PRO G 376 14.606 18.224 -30.892 1.00 7.90 C
ATOM 2391 CB PRO G 376 13.837 18.238 -32.211 1.00 7.90 C
ATOM 2392 CG PRO G 376 12.558 17.556 -31.891 1.00 7.97 C
ATOM 2393 CD PRO G 376 12.913 16.481 -30.912 1.00 7.40 C
ATOM 2394 C PRO G 376 14.294 19.486 -30.095 1.00 8.35 C
ATOM 2395 O PRO G 376 13.205 19.611 -29.533 1.00 8.71 O
ATOM 2396 N SER G 377 15.206 20.451 -30.137 1.00 9.11 N
ATOM 2397 CA SER G 377 14.990 21.743 -29.494 1.00 9.91 C
ATOM 2398 CB SER G 377 16.155 22.691 -29.792 1.00 10.23 C
ATOM 2399 OG SER G 377 17.300 21.973 -30.222 1.00 10.90 O
ATOM 2400 C SER G 377 13.673 22.377 -29.937 1.00 10.14 C
ATOM 2401 O SER G 377 13.295 23.444 -29.450 1.00 10.08 O
ATOM 2402 N GLU G 378 13.011 21.749 -30.906 1.00 10.71 N
ATOM 2403 CA GLU G 378 11.714 22.222 -31.382 1.00 11.40 C
ATOM 2404 CB GLU G 378 11.357 21.569 -32.721 1.00 11.65 C
ATOM 2405 CG GLU G 378 11.978 22.250 -33.933 1.00 13.46 C
ATOM 2406 CD GLU G 378 13.490 22.160 -33.938 1.00 16.20 C
ATOM 2407 OE1 GLU G 378 14.046 21.522 -33.021 1.00 15.73 O
ATOM 2408 OE2 GLU G 378 14.121 22.732 -34.852 1.00 18.38 O
ATOM 2409 C GLU G 378 10.623 21.944 -30.353 1.00 11.27 C
ATOM 2410 O GLU G 378 9.561 22.565 -30.377 1.00 11.28 O
ATOM 2411 N VAL G 379 10.909 21.031 -29.430 1.00 11.31 N
ATOM 2412 CA VAL G 379 10.053 20.819 -28.269 1.00 11.59 C
ATOM 2413 CB VAL G 379 10.737 19.926 -27.216 1.00 11.27 C
ATOM 2414 CGI VAL G 379 10.100 20.131 -25.850 1.00 11.60 C
ATOM 2415 CG2 VAL G 379 10.667 18.465 -27.631 1.00 11.54 C
ATOM 2416 C VAL G 379 9.665 22.144 -27.620 1.00 12.16 C
ATOM 2417 O VAL G 379 8.541 22.307 -27.146 1.00 12.51 O
ATOM 2418 N ASN G 380 10.587 23.100 -27.634 1.00 12.98 N
ATOM 2419 CA ASN G 380 10.415 24.335 -26.878 1.00 14.00 C
ATOM 2420 CB ASN G 380 11.703 25.156 -26.884 1.00 14.59 C
ATOM 2421 CG ASN G 380 12.829 24.474 -26.138 1.00 17.09 C
ATOM 2422 OD1 ASN G 380 13.073 24.764 -24.966 1.00 20.41 O
ATOM 2423 ND2 ASN G 380 13.432 23.471 -26.767 1.00 18.86 N
ATOM 2424 C ASN G 380 9.242 25.192 -27.349 1.00 13.96 C
ATOM 2425 O ASN G 380 8.640 25.915 -26.555 1.00 14.38 O
ATOM 2426 N LEU G 381 8.994 25.197 -28.655 1.00 13.61 N
ATOM 2427 CA LEU G 381 7.918 26.006 -29.220 1.00 13.72 C
ATOM 2428 CB LEU G 381 7.854 25.829 -30.737 1.00 13.79 C
ATOM 2429 CG LEU G 381 9.183 25.514 -31.424 1.00 14.92 C
ATOM 2430 CD1 LEU G 381 8.969 25.231 -32.902 1.00 15.56 C
ATOM 2431 CD2 LEU G 381 10.171 26.655 -31.230 1.00 15.78 C
ATOM 2432 C LEU G 381 6.590 25.603 -28.600 1.00 13.62 C
ATOM 2433 O LEU G 381 5.600 26.331 -28.682 1.00 13.57 O
ATOM 2434 N CYS G 382 6.590 24.440 -27.963 1.00 13.47 N
ATOM 2435 CA CYS G 382 5.383 23.876 -27.392 1.00 13.57 C
ATOM 2436 CB CYS G 382 5.572 22.380 -27.161 1.00 13.62 C ATOM 2437 SG CYS G 382 4.877 21.350 -28.457 1.00 15.64 S
ATOM 2438 C CYS G 382 5.019 24.572 -26.085 1.00 13.33 C
ATOM 2439 O CYS G 382 3.861 24.561 -25.669 1.00 13.57 O
ATOM 2440 N ASN G 383 5.999 25.236 -25.480 1.00 13.21 N
ATOM 2441 CA ASN G 383 5.736 26.114 -24.345 1.00 13.22 C
ATOM 2442 CB ASN G 383 7.046 26.621 -23.742 1.00 13.18 C
ATOM 2443 CG ASN G 383 7.979 25.498 -23.349 1.00 13.42 C
ATOM 2444 OD1 ASN G 383 7.560 24.505 -22.755 1.00 13.68 O
ATOM 2445 ND2 ASN G 383 9.255 25.648 -23.682 1.00 14.32 N
ATOM 2446 C ASN G 383 4.872 27.298 -24.747 1.00 13.28 C
ATOM 2447 O ASN G 383 4.229 27.925 -23.906 1.00 13.50 O
ATOM 2448 N VAL G 384 5.000 27.699 -26.005 1.00 13.24 N
ATOM 2449 CA VAL G 384 4.313 28.878 -26.496 1.00 13.29 C
ATOM 2450 CB VAL G 384 5.234 29.751 -27.370 1.00 13.28 C
ATOM 2451 CGI VAL G 384 4.414 30.627 -28.302 1.00 13.73 C
ATOM 2452 CG2 VAL G 384 6.145 30.599 -26.495 1.00 12.76 C
ATOM 2453 C VAL G 384 3.045 28.514 -27.261 1.00 13.57 C
ATOM 2454 O VAL G 384 2.050 29.233 -27.188 1.00 13.31 O
ATOM 2455 N ASP G 385 3.056 27.383 -27.960 1.00 14.07 N
ATOM 2456 CA ASP G 385 1.999 27.121 -28.932 1.00 14.61 C
ATOM 2457 CB ASP G 385 2.452 27.379 -30.366 1.00 14.71 C
ATOM 2458 CG ASP G 385 1.436 28.182 -31.154 1.00 16.69 C
ATOM 2459 OD1 ASP G 385 0.270 28.259 -30.713 1.00 18.63 O
ATOM 2460 OD2 ASP G 385 1.807 28.759 -32.197 1.00 19.10 O
ATOM 2461 C ASP G 385 1.170 25.841 -28.816 1.00 14.63 C
ATOM 2462 O ASP G 385 -0.043 25.880 -29.017 1.00 14.34 O
ATOM 2463 N ILE G 386 1.820 24.697 -28.624 1.00 14.54 N
ATOM 2464 CA ILE G 386 1.116 23.413 -28.688 1.00 14.46 C
ATOM 2465 CB ILE G 386 -0.230 23.466 -27.928 1.00 13.83 C
ATOM 2466 CGI ILE G 386 -0.004 23.458 -26.415 1.00 13.44 C
ATOM 2467 CD1 ILE G 386 -1.184 23.970 -25.612 1.00 12.39 C
ATOM 2468 CG2 ILE G 386 -1.119 22.301 -28.341 1.00 13.51 C
ATOM 2469 C ILE G 386 0.791 23.079 -30.134 1.00 14.73 C
ATOM 2470 O ILE G 386 1.282 22.092 -30.683 1.00 14.68 O
ATOM 2471 N PHE G 387 -0.191 23.797 -30.667 1.00 14.71 N
ATOM 2472 CA PHE G 387 -0.462 23.794 -32.092 1.00 14.78 C
ATOM 2473 CB PHE G 387 -1.889 24.254 -32.366 1.00 14.77 C
ATOM 2474 CG PHE G 387 -2.906 23.607 -31.479 1.00 14.75 C
ATOM 2475 CD 1 PHE G 387 -3.418 24.287 -30.390 1.00 15.03 C
ATOM 2476 CE1 PHE G 387 -4.333 23.684 -29.549 1.00 14.62 C
ATOM 2477 CZ PHE G 387 -4.683 22.364 -29.747 1.00 14.55 C
ATOM 2478 CE2 PHE G 387 -4.113 21.651 -30.780 1.00 14.68 C
ATOM 2479 CD2 PHE G 387 -3.206 22.265 -31.621 1.00 14.61 C
ATOM 2480 C PHE G 387 0.526 24.670 -32.837 1.00 14.91 C
ATOM 2481 O PHE G 387 0.658 25.862 -32.559 1.00 14.86 O
ATOM 2482 N ASN G 388 1.361 24.007 -33.621 1.00 15.11 N
ATOM 2483 CA ASN G 388 2.352 24.663 -34.443 1.00 15.38 C
ATOM 2484 CB ASN G 388 3.362 25.405 -33.570 1.00 14.86 C
ATOM 2485 CG ASN G 388 4.097 24.480 -32.625 1.00 14.86 C
ATOM 2486 OD1 ASN G 388 5.078 23.840 -33.004 1.00 12.80 O
ATOM 2487 ND2 ASN G 388 3.575 24.338 -31.413 1.00 15.97 N
ATOM 2488 C ASN G 388 3.057 23.576 -35.229 1.00 16.11 C
ATOM 2489 O ASN G 388 3.416 22.537 -34.670 1.00 15.92 O
ATOM 2490 N PRO G 389 3.071 23.722 -36.557 1.00 16.99 N
ATOM 2491 CA PRO G 389 4.005 22.905 -37.315 1.00 17.40 C
ATOM 2492 CB PRO G 389 4.169 23.689 -38.618 1.00 17.72 C
ATOM 2493 CG PRO G 389 3.905 25.099 -38.236 1.00 17.47 C
ATOM 2494 CD PRO G 389 2.825 25.023 -37.203 1.00 17.05 C
ATOM 2495 C PRO G 389 5.338 22.827 -36.583 1.00 17.86 C
ATOM 2496 O PRO G 389 5.638 23.687 -35.755 1.00 18.45 O ATOM 2497 N LYS G 390 6.139 21.817 -36.902 1.00 17.97 N
ATOM 2498 CA LYS G 390 7.443 21.658 -36.273 1.00 18.06 C
ATOM 2499 CB LYS G 390 7.947 22.997 -35.730 1.00 17.92 C
ATOM 2500 CG LYS G 390 8.466 23.945 -36.798 1.00 18.58 C
ATOM 2501 CD LYS G 390 9.962 23.777 -37.006 1.00 20.61 C
ATOM 2502 CE LYS G 390 10.562 24.985 -37.707 1.00 21.48 C
ATOM 2503 NZ LYS G 390 10.191 25.032 -39.148 1.00 23.16 N
ATOM 2504 C LYS G 390 7.398 20.623 -35.156 1.00 18.01 C
ATOM 2505 O LYS G 390 8.177 19.670 -35.152 1.00 18.43 O
ATOM 2506 N TY G 391 6.481 20.805 -34.213 1.00 17.68 N
ATOM 2507 CA TYR G 391 6.234 19.780 -33.211 1.00 17.33 C
ATOM 2508 CB TYR G 391 6.862 20.158 -31.872 1.00 17.42 C
ATOM 2509 CG TYR G 391 7.485 18.979 -31.173 1.00 17.27 C
ATOM 2510 CD1 TYR G 391 8.188 18.028 -31.898 1.00 17.29 C
ATOM 2511 CE1 TYR G 391 8.672 16.885 -31.297 1.00 17.32 C
ATOM 2512 CZ TYR G 391 8.408 16.653 -29.965 1.00 16.51 C
ATOM 2513 OH TYR G 391 8.940 15.541 -29.354 1.00 16.65 O
ATOM 2514 CE2 TYR G 391 7.656 17.552 -29.237 1.00 16.52 C
ATOM 2515 CD2 TYR G 391 7.167 18.687 -29.853 1.00 17.24 C
ATOM 2516 C TYR G 391 4.757 19.471 -33.034 1.00 17.43 C
ATOM 2517 O TYR G 391 3.984 20.332 -32.614 1.00 17.70 O
ATOM 2518 N ASP G 392 4.398 18.202 -33.196 1.00 17.56 N
ATOM 2519 CA ASP G 392 3.191 17.693 -32.565 1.00 17.69 C
ATOM 2520 CB ASP G 392 2.610 16.498 -33.322 1.00 17.89 C
ATOM 2521 CG ASP G 392 3.494 16.038 -34.456 1.00 18.86 C
ATOM 2522 OD1 ASP G 392 4.636 15.613 -34.185 1.00 20.34 O
ATOM 2523 OD2 ASP G 392 3.008 15.998 -35.604 1.00 18.51 O
ATOM 2524 C ASP G 392 3.428 17.344 -31.107 1.00 17.11 C
ATOM 2525 O ASP G 392 4.495 16.860 -30.731 1.00 17.04 O
ATOM 2526 N CYS G 393 2.452 17.684 -30.280 1.00 16.33 N
ATOM 2527 CA CYS G 393 2.723 18.199 -28.957 1.00 16.17 C
ATOM 2528 CB CYS G 393 2.419 19.693 -28.910 1.00 16.11 C
ATOM 2529 SG CYS G 393 3.237 20.556 -27.570 1.00 20.23 S
ATOM 2530 C CYS G 393 1.812 17.471 -27.995 1.00 15.37 C
ATOM 2531 O CYS G 393 0.592 17.525 -28.139 1.00 15.15 O
ATOM 2532 N LYS G 394 2.399 16.618 -27.168 1.00 14.91 N
ATOM 2533 CA LYS G 394 1.608 15.678 -26.398 1.00 14.50 C
ATOM 2534 CB LYS G 394 2.495 14.607 -25.771 1.00 14.60 C
ATOM 2535 CG LYS G 394 3.531 14.052 -26.730 1.00 16.44 C
ATOM 2536 CD LYS G 394 4.034 12.699 -26.272 1.00 20.45 C
ATOM 2537 CE LYS G 394 4.868 12.823 -25.009 1.00 23.05 C
ATOM 2538 NZ LYS G 394 4.057 13.264 -23.841 1.00 24.13 N
ATOM 2539 C LYS G 394 0.767 16.388 -25.344 1.00 14.00 C
ATOM 2540 O LYS G 394 1.249 17.268 -24.630 1.00 14.14 O
ATOM 2541 N ILE G 395 -0.486 15.955 -25.236 1.00 13.28 N
ATOM 2542 CA ILE G 395 -1.587 16.768 -24.725 1.00 12.89 C
ATOM 2543 CB ILE G 395 -2.234 17.626 -25.843 1.00 12.75 C
ATOM 2544 CGI ILE G 395 -1.418 18.897 -26.097 1.00 13.58 C
ATOM 2545 CD1 ILE G 395 -1.635 19.507 -27.466 1.00 15.33 C
ATOM 2546 CG2 ILE G 395 -3.669 17.980 -25.477 1.00 12.16 C
ATOM 2547 C ILE G 395 -2.631 15.761 -24.284 1.00 13.15 C
ATOM 2548 O ILE G 395 -2.826 14.746 -24.951 1.00 13.45 O
ATOM 2549 N MET G 396 -3.440 16.127 -23.303 1.00 13.06 N
ATOM 2550 CA MET G 396 -4.668 15.392 -23.085 1.00 13.00 C
ATOM 2551 CB MET G 396 -4.579 14.539 -21.824 1.00 13.34 C
ATOM 2552 CG MET G 396 -5.208 15.167 -20.600 1.00 14.30 C
ATOM 2553 SD MET G 396 -5.006 14.087 -19.179 1.00 18.50 S
ATOM 2554 CE MET G 396 -3.465 13.282 -19.611 1.00 17.80 C
ATOM 2555 C MET G 396 -5.889 16.288 -23.050 1.00 12.96 C
ATOM 2556 O MET G 396 -5.811 17.453 -22.663 1.00 13.04 O ATOM 2557 N TH G 397 -7.037 15.686 -23.336 1.00 12.78 N
ATOM 2558 CA THR G 397 -8.200 16.415 -23.815 1.00 12.51 C
ATOM 2559 CB THR G 397 -8.653 15.898 -25.193 1.00 12.39 C
ATOM 2560 OG1 THR G 397 -7.837 16.481 -26.216 1.00 12.50 O
ATOM 2561 CG2 THR G 397 -10.114 16.250 -25.447 1.00 12.55 C
ATOM 2562 C THR G 397 -9.343 16.223 -22.834 1.00 12.58 C
ATOM 2563 O THR G 397 -9.563 15.117 -22.340 1.00 12.88 O
ATOM 2564 N SER G 398 -10.157 17.255 -22.663 1.00 12.55 N
ATOM 2565 CA SER G 398 -11.452 17.049 -22.049 1.00 12.76 C
ATOM 2566 CB SER G 398 -11.323 16.949 -20.527 1.00 12.52 C
ATOM 2567 OG SER G 398 -12.592 16.781 -19.919 1.00 12.72 O
ATOM 2568 C SER G 398 -12.478 18.103 -22.410 1.00 12.99 C
ATOM 2569 O SER G 398 -12.269 18.917 -23.311 1.00 13.13 O
ATOM 2570 N LYS G 399 -13.435 18.245 -21.504 1.00 13.01 N
ATOM 2571 CA LYS G 399 -14.399 19.325 -21.544 1.00 13.29 C
ATOM 2572 CB LYS G 399 -15.777 18.777 -21.908 1.00 13.79 C
ATOM 2573 CG LYS G 399 -16.044 18.714 -23.399 1.00 14.34 C
ATOM 2574 CD LYS G 399 -16.965 19.840 -23.833 1.00 16.43 C
ATOM 2575 CE LYS G 399 -17.285 19.750 -25.315 1.00 17.37 C
ATOM 2576 NZ LYS G 399 -17.904 21.003 -25.828 1.00 16.62 N
ATOM 2577 C LYS G 399 -14.460 19.996 -20.179 1.00 13.09 C
ATOM 2578 O LYS G 399 -14.619 21.213 -20.084 1.00 12.87 O
ATOM 2579 N THR G 400 -14.348 19.198 -19.123 1.00 13.04 N
ATOM 2580 CA THR G 400 -14.535 19.715 -17.776 1.00 13.38 C
ATOM 2581 CB THR G 400 -15.257 18.709 -16.861 1.00 13.74 C
ATOM 2582 OG1 THR G 400 -15.856 17.678 -17.655 1.00 14.38 O
ATOM 2583 CG2 THR G 400 -16.337 19.409 -16.051 1.00 14.32 C
ATOM 2584 C THR G 400 -13.226 20.134 -17.120 1.00 13.20 C
ATOM 2585 O THR G 400 -12.169 19.594 -17.445 1.00 13.12 O
ATOM 2586 N ASP G 401 -13.378 20.770 -15.963 1.00 12.97 N
ATOM 2587 CA ASP G 401 -12.358 21.654 -15.396 1.00 12.50 C
ATOM 2588 CB ASP G 401 -13.014 22.766 -14.590 1.00 12.73 C
ATOM 2589 CG ASP G 401 -12.765 24.122 -15.183 1.00 13.98 C
ATOM 2590 OD1 ASP G 401 -13.073 24.301 -16.380 1.00 16.55 O
ATOM 2591 OD2 ASP G 401 -12.168 24.973 -14.492 1.00 14.80 O
ATOM 2592 C ASP G 401 -11.269 21.029 -14.529 1.00 12.13 C
ATOM 2593 O ASP G 401 -11.547 20.130 -13.729 1.00 12.31 O
ATOM 2594 N VAL G 402 -10.200 21.822 -14.390 1.00 11.49 N
ATOM 2595 CA VAL G 402 -9.667 22.261 -13.080 1.00 10.74 C
ATOM 2596 CB VAL G 402 -8.369 21.519 -12.744 1.00 10.60 C
ATOM 2597 CGI VAL G 402 -7.449 22.413 -11.914 1.00 11.26 C
ATOM 2598 CG2 VAL G 402 -8.672 20.211 -12.019 1.00 10.99 C
ATOM 2599 C VAL G 402 -9.360 23.769 -12.883 1.00 10.24 C
ATOM 2600 O VAL G 402 -9.387 24.539 -13.845 1.00 10.30 O
ATOM 2601 N SER G 403 -8.762 24.081 -11.719 1.00 9.76 N
ATOM 2602 CA SER G 403 -8.493 25.474 -11.271 1.00 9.18 C
ATOM 2603 CB SER G 403 -9.790 26.197 -10.893 1.00 9.41 C
ATOM 2604 OG SER G 403 -10.714 25.319 -10.274 1.00 10.82 O
ATOM 2605 C SER G 403 -7.394 25.745 -10.199 1.00 8.51 C
ATOM 2606 O SER G 403 -7.465 25.236 -9.076 1.00 8.30 O
ATOM 2607 N SER G 404 -6.524 26.720 -10.502 1.00 8.35 N
ATOM 2608 CA SER G 404 -5.785 27.535 -9.507 1.00 8.18 C
ATOM 2609 CB SER G 404 -4.851 26.657 -8.669 1.00 8.18 C
ATOM 2610 OG SER G 404 -3.507 26.782 -9.100 1.00 8.83 O
ATOM 2611 C SER G 404 -4.979 28.665 -10.187 1.00 7.62 C
ATOM 2612 O SER G 404 -5.183 28.942 -11.369 1.00 7.57 O
ATOM 2613 N SER G 405 -4.041 29.282 -9.462 1.00 7.08 N
ATOM 2614 CA SER G 405 -3.258 30.409 -10.003 1.00 6.53 C
ATOM 2615 CB SER G 405 -3.844 31.752 -9.555 1.00 6.42 C
ATOM 2616 OG SER G 405 -2.883 32.790 -9.662 1.00 5.66 O ATOM 2617 C SE G 405 -1.756 30.364 -9.693 1.00 6.28 C
ATOM 2618 O SER G 405 -1.338 29.830 -8.666 1.00 5.98 O
ATOM 2619 N VAL G 406 -0.980 31.079 -10.506 1.00 6.22 N
ATOM 2620 CA VAL G 406 0.479 31.053 -10.436 1.00 6.50 C
ATOM 2621 CB VAL G 406 1.068 30.055 -11.453 1.00 6.45 C
ATOM 2622 CGI VAL G 406 2.518 29.743 -11.116 1.00 7.66 C
ATOM 2623 CG2 VAL G 406 0.236 28.783 -11.495 1.00 7.38 C
ATOM 2624 C VAL G 406 1.029 32.438 -10.760 1.00 6.24 C
ATOM 2625 O VAL G 406 0.763 32.981 -11.832 1.00 6.14 O
ATOM 2626 N ILE G 407 1.803 33.001 -9.840 1.00 6.32 N
ATOM 2627 CA ILE G 407 2.315 34.354 -10.014 1.00 6.60 C
ATOM 2628 CB ILE G 407 2.445 35.097 -8.674 1.00 6.27 C
ATOM 2629 CG1 ILE G 407 1.070 35.564 -8.194 1.00 6.19 C
ATOM 2630 CD1 ILE G 407 1.086 36.200 -6.824 1.00 8.34 C
ATOM 2631 CG2 ILE G 407 3.391 36.282 -8.813 1.00 6.42 C
ATOM 2632 C ILE G 407 3.657 34.361 -10.728 1.00 7.20 C
ATOM 2633 O ILE G 407 4.576 33.631 -10.356 1.00 7.42 O
ATOM 2634 N THR G 408 3.797 35.273 -11.682 1.00 7.57 N
ATOM 2635 CA THR G 408 4.983 35.324 -12.517 1.00 8.19 C
ATOM 2636 CB THR G 408 4.622 35.305 -14.011 1.00 8.15 C
ATOM 2637 OG1 THR G 408 3.785 36.426 -14.318 1.00 8.88 O
ATOM 2638 CG2 THR G 408 3.891 34.020 -14.364 1.00 7.93 C
ATOM 2639 C THR G 408 5.804 36.569 -12.225 1.00 8.55 C
ATOM 2640 O THR G 408 5.418 37.408 -11.410 1.00 9.07 O
ATOM 2641 N SER G 409 6.918 36.698 -12.935 1.00 8.70 N
ATOM 2642 CA SER G 409 7.843 37.799 -12.723 1.00 9.20 C
ATOM 2643 CB SER G 409 9.067 37.643 -13.628 1.00 9.72 C
ATOM 2644 OG SER G 409 9.571 36.320 -13.581 1.00 10.75 O
ATOM 2645 C SER G 409 7.153 39.125 -13.007 1.00 9.01 C
ATOM 2646 O SER G 409 7.433 40.135 -12.359 1.00 9.02 O
ATOM 2647 N LEU G 410 6.259 39.118 -13.990 1.00 8.91 N
ATOM 2648 CA LEU G 410 5.790 40.352 -14.604 1.00 9.29 C
ATOM 2649 CB LEU G 410 6.438 40.546 -15.976 1.00 9.61 C
ATOM 2650 CG LEU G 410 7.245 41.834 -16.150 1.00 9.70 C
ATOM 2651 CD1 LEU G 410 8.433 41.858 -15.200 1.00 11.11 C
ATOM 2652 CD2 LEU G 410 7.705 41.994 -17.591 1.00 9.16 C
ATOM 2653 C LEU G 410 4.272 40.351 -14.729 1.00 9.12 C
ATOM 2654 O LEU G 410 3.683 41.248 -15.332 1.00 9.08 O
ATOM 2655 N GLY G 411 3.646 39.332 -14.154 1.00 9.03 N
ATOM 2656 CA GLY G 411 2.203 39.315 -13.982 1.00 8.44 C
ATOM 2657 C GLY G 411 1.765 38.048 -13.284 1.00 7.91 C
ATOM 2658 O GLY G 411 2.435 37.568 -12.369 1.00 7.85 O
ATOM 2659 N ALA G 412 0.674 37.465 -13.763 1.00 7.30 N
ATOM 2660 CA ALA G 412 0.129 36.264 -13.153 1.00 6.92 C
ATOM 2661 CB ALA G 412 -0.742 36.623 -11.960 1.00 6.90 C
ATOM 2662 C ALA G 412 -0.661 35.453 -14.166 1.00 6.99 C
ATOM 2663 O ALA G 412 -1.257 36.002 -15.093 1.00 6.94 O
ATOM 2664 N ILE G 413 -0.621 34.137 -14.006 1.00 7.29 N
ATOM 2665 CA ILE G 413 -1.478 33.244 -14.766 1.00 7.49 C
ATOM 2666 CB ILE G 413 -0.711 31.990 -15.201 1.00 7.24 C
ATOM 2667 CG1 ILE G 413 0.314 32.350 -16.278 1.00 7.18 C
ATOM 2668 CD1 ILE G 413 0.927 31.150 -16.973 1.00 7.70 C
ATOM 2669 CG2 ILE G 413 -1.674 30.916 -15.688 1.00 7.70 C
ATOM 2670 C ILE G 413 -2.657 32.822 -13.908 1.00 7.94 C
ATOM 2671 O ILE G 413 -2.544 32.749 -12.685 1.00 8.39 O
ATOM 2672 N VAL G 414 -3.782 32.521 -14.544 1.00 8.22 N
ATOM 2673 CA VAL G 414 -4.909 31.961 -13.816 1.00 8.77 C
ATOM 2674 CB VAL G 414 -5.865 33.050 -13.296 1.00 8.57 C
ATOM 2675 CGI VAL G 414 -6.133 34.085 -14.376 1.00 9.12 C
ATOM 2676 CG2 VAL G 414 -7.162 32.427 -12.803 1.00 8.90 C ATOM 2677 C VAL G 414 -5.674 30.901 -14.594 1.00 8.92 C
ATOM 2678 O VAL G 414 -6.114 31.129 -15.722 1.00 9.00 O
ATOM 2679 N SE G 415 -5.750 29.714 -14.004 1.00 8.97 N
ATOM 2680 CA SER G 415 -6.472 28.598 -14.592 1.00 9.02 C
ATOM 2681 CB SER G 415 -5.625 27.328 -14.520 1.00 8.98 C
ATOM 2682 OG SER G 415 -4.353 27.532 -15.108 1.00 9.54 O
ATOM 2683 C SER G 415 -7.791 28.390 -13.864 1.00 9.36 C
ATOM 2684 O SER G 415 -7.818 27.884 -12.742 1.00 9.61 O
ATOM 2685 N CYS G 416 -8.854 28.950 -14.430 1.00 9.57 N
ATOM 2686 CA CYS G 416 -10.175 28.857 -13.831 1.00 9.61 C
ATOM 2687 CB CYS G 416 -10.895 30.201 -13.912 1.00 9.62 C
ATOM 2688 SG CYS G 416 -12.025 30.497 -12.543 1.00 11.33 S
ATOM 2689 C CYS G 416 -11.000 27.796 -14.534 1.00 9.61 C
ATOM 2690 O CYS G 416 -11.361 27.950 -15.700 1.00 9.80 O
ATOM 2691 N TYR G 417 -11.298 26.717 -13.821 1.00 9.48 N
ATOM 2692 CA TYR G 417 -11.930 25.566 -14.438 1.00 9.28 C
ATOM 2693 CB TYR G 417 -10.888 24.501 -14.782 1.00 9.17 C
ATOM 2694 CG TYR G 417 -10.011 24.860 -15.962 1.00 8.71 C
ATOM 2695 CD1 TYR G 417 -8.661 24.543 -15.968 1.00 8.54 C
ATOM 2696 CE1 TYR G 417 -7.857 24.869 -17.043 1.00 9.56 C
ATOM 2697 CZ TYR G 417 -8.407 25.480 -18.149 1.00 9.83 C
ATOM 2698 OH TYR G 417 -7.602 25.828 -19.207 1.00 10.51 O
ATOM 2699 CE2 TYR G 417 -9.738 25.830 -18.159 1.00 9.36 C
ATOM 2700 CD2 TYR G 417 -10.532 25.522 -17.068 1.00 8.95 C
ATOM 2701 C TYR G 417 -13.034 24.978 -13.566 1.00 9.35 C
ATOM 2702 O TYR G 417 -13.171 25.332 -12.395 1.00 9.11 O
ATOM 2703 N GLY G 418 -13.848 24.115 -14.165 1.00 9.71 N
ATOM 2704 CA GLY G 418 -14.993 23.534 -13.481 1.00 9.95 C
ATOM 2705 C GLY G 418 -15.925 24.594 -12.936 1.00 10.09 C
ATOM 2706 O GLY G 418 -16.170 25.611 -13.585 1.00 10.17 O
ATOM 2707 N LYS G 419 -16.323 24.426 -11.681 1.00 10.17 N
ATOM 2708 CA LYS G 419 -17.328 25.289 -11.075 1.00 10.50 C
ATOM 2709 CB LYS G 419 -18.123 24.523 -10.015 1.00 11.09 C
ATOM 2710 CG LYS G 419 -19.389 23.867 -10.538 1.00 12.94 C
ATOM 2711 CD LYS G 419 -20.304 23.450 -9.397 1.00 15.52 C
ATOM 2712 CE LYS G 419 -21.702 23.127 -9.899 1.00 17.07 C
ATOM 2713 NZ LYS G 419 -21.688 22.058 -10.936 1.00 19.30 N
ATOM 2714 C LYS G 419 -16.737 26.560 -10.464 1.00 10.23 C
ATOM 2715 O LYS G 419 -17.451 27.325 -9.817 1.00 10.58 O
ATOM 2716 N THR G 420 -15.429 26.755 -10.607 1.00 10.10 N
ATOM 2717 CA THR G 420 -14.730 27.754 -9.801 1.00 9.74 C
ATOM 2718 CB THR G 420 -13.232 27.432 -9.651 1.00 9.28 C
ATOM 2719 OG1 THR G 420 -12.992 26.073 -10.034 1.00 9.21 O
ATOM 2720 CG2 THR G 420 -12.788 27.635 -8.209 1.00 9.03 C
ATOM 2721 C THR G 420 -14.900 29.178 -10.329 1.00 9.95 C
ATOM 2722 O THR G 420 -15.143 29.387 -11.518 1.00 10.35 O
ATOM 2723 N LYS G 421 -14.816 30.149 -9.424 1.00 10.07 N
ATOM 2724 CA LYS G 421 -14.950 31.559 -9.780 1.00 10.21 C
ATOM 2725 CB LYS G 421 -15.973 32.239 -8.867 1.00 10.30 C
ATOM 2726 CG LYS G 421 -17.368 32.341 -9.457 1.00 12.43 C
ATOM 2727 CD LYS G 421 -18.345 32.931 -8.452 1.00 15.12 C
ATOM 2728 CE LYS G 421 -19.766 32.470 -8.727 1.00 15.21 C
ATOM 2729 NZ LYS G 421 -20.617 32.544 -7.508 1.00 15.98 N
ATOM 2730 C LYS G 421 -13.608 32.271 -9.658 1.00 10.09 C
ATOM 2731 O LYS G 421 -12.911 32.125 -8.653 1.00 10.36 O
ATOM 2732 N CYS G 422 -13.271 33.085 -10.653 1.00 9.81 N
ATOM 2733 CA CYS G 422 -12.006 33.808 -10.631 1.00 9.56 C
ATOM 2734 CB CYS G 422 -10.953 33.092 -11.475 1.00 9.72 C
ATOM 2735 SG CYS G 422 -10.831 31.329 -11.131 1.00 11.42 S
ATOM 2736 C CYS G 422 -12.126 35.268 -11.044 1.00 9.18 C ATOM 2737 O CYS G 422 -12.927 35.624 -11.909 1.00 9.27 O
ATOM 2738 N TH G 423 -11.232 36.084 -10.497 1.00 8.93 N
ATOM 2739 CA THR G 423 -11.422 37.525 -10.427 1.00 8.64 C
ATOM 2740 CB THR G 423 -12.062 37.938 -9.088 1.00 8.32 C
ATOM 2741 OG1 THR G 423 -13.201 37.111 -8.821 1.00 7.97 O
ATOM 2742 CG2 THR G 423 -12.494 39.396 -9.130 1.00 8.36 C
ATOM 2743 C THR G 423 -10.059 38.190 -10.513 1.00 8.86 C
ATOM 2744 O THR G 423 -9.183 37.928 -9.688 1.00 9.26 O
ATOM 2745 N ALA G 424 -9.913 39.124 -11.444 1.00 8.74 N
ATOM 2746 CA ALA G 424 -8.792 40.052 -11.408 1.00 8.79 C
ATOM 2747 CB ALA G 424 -8.164 40.180 -12.786 1.00 8.94 C
ATOM 2748 C ALA G 424 -9.240 41.414 -10.894 1.00 8.84 C
ATOM 2749 O ALA G 424 -10.084 42.070 -11.504 1.00 9.24 O
ATOM 2750 N SER G 425 -8.669 41.836 -9.771 1.00 8.81 N
ATOM 2751 CA SER G 425 -9.007 43.124 -9.180 1.00 8.85 C
ATOM 2752 CB SER G 425 -9.483 42.942 -7.737 1.00 8.94 C
ATOM 2753 OG SER G 425 -9.918 41.613 -7.507 1.00 7.69 O
ATOM 2754 C SER G 425 -7.815 44.072 -9.222 1.00 9.01 C
ATOM 2755 O SER G 425 -6.669 43.651 -9.059 1.00 8.63 O
ATOM 2756 N ASN G 426 -8.089 45.354 -9.441 1.00 9.54 N
ATOM 2757 CA ASN G 426 -7.033 46.328 -9.686 1.00 10.19 C
ATOM 2758 CB ASN G 426 -7.537 47.462 -10.583 1.00 9.77 C
ATOM 2759 CG ASN G 426 -8.273 48.540 -9.808 1.00 9.43 C
ATOM 2760 OD1 ASN G 426 -8.253 48.561 -8.578 1.00 9.01 O
ATOM 2761 ND2 ASN G 426 -8.938 49.436 -10.528 1.00 9.01 N
ATOM 2762 C ASN G 426 -6.434 46.891 -8.400 1.00 11.16 C
ATOM 2763 O ASN G 426 -6.629 46.340 -7.316 1.00 11.06 O
ATOM 2764 N LYS G 427 -5.658 47.961 -8.543 1.00 12.38 N
ATOM 2765 CA LYS G 427 -5.016 48.627 -7.413 1.00 13.52 C
ATOM 2766 CB LYS G 427 -4.455 49.981 -7.851 1.00 14.00 C
ATOM 2767 CG LYS G 427 -2.987 49.956 -8.233 1.00 16.18 C
ATOM 2768 CD LYS G 427 -2.434 51.366 -8.365 1.00 18.24 C
ATOM 2769 CE LYS G 427 -0.955 51.413 -8.022 1.00 19.72 C
ATOM 2770 NZ LYS G 427 -0.707 51.116 -6.584 1.00 21.43 N
ATOM 2771 C LYS G 427 -5.976 48.829 -6.245 1.00 13.71 C
ATOM 2772 O LYS G 427 -5.630 48.562 -5.093 1.00 13.63 O
ATOM 2773 N ASN G 428 -7.119 49.443 -6.535 1.00 14.28 N
ATOM 2774 CA ASN G 428 -8.080 49.830 -5.505 1.00 14.60 C
ATOM 2775 CB ASN G 428 -9.009 50.934 -6.020 1.00 14.57 C
ATOM 2776 CG ASN G 428 -8.353 51.808 -7.071 1.00 13.24 C
ATOM 2777 OD1 ASN G 428 -7.314 52.420 -6.823 1.00 9.74 O
ATOM 2778 ND2 ASN G 428 -9.009 51.946 -8.217 1.00 12.83 N
ATOM 2779 C ASN G 428 -8.914 48.658 -4.994 1.00 14.83 C
ATOM 2780 O ASN G 428 -9.645 48.793 -4.013 1.00 15.25 O
ATOM 2781 N ARG G 429 -8.920 47.564 -5.750 1.00 14.78 N
ATOM 2782 CA ARG G 429 -9.725 46.395 -5.407 1.00 14.74 C
ATOM 2783 CB ARG G 429 -10.088 46.405 -3.920 1.00 14.93 C
ATOM 2784 CG ARG G 429 -8.949 45.999 -2.999 1.00 16.26 C
ATOM 2785 CD ARG G 429 -8.954 44.502 -2.732 1.00 19.79 C
ATOM 2786 NE ARG G 429 -7.694 44.046 -2.152 1.00 22.68 N
ATOM 2787 CZ ARG G 429 -7.270 44.369 -0.935 1.00 23.54 C
ATOM 2788 NH1 ARG G 429 -7.998 45.170 -0.168 1.00 22.87 N
ATOM 2789 NH2 ARG G 429 -6.107 43.912 -0.492 1.00 23.53 N
ATOM 2790 C ARG G 429 -10.989 46.304 -6.256 1.00 14.35 C
ATOM 2791 O ARG G 429 -11.653 45.268 -6.287 1.00 14.62 O
ATOM 2792 N GLY G 430 -11.306 47.386 -6.961 1.00 13.67 N
ATOM 2793 CA GLY G 430 -12.201 47.311 -8.110 1.00 12.80 C
ATOM 2794 C GLY G 430 -11.870 46.136 -9.009 1.00 12.11 C
ATOM 2795 O GLY G 430 -10.707 45.903 -9.338 1.00 12.18 O
ATOM 2796 N ILE G 431 -12.892 45.374 -9.380 1.00 11.58 N ATOM 2797 CA ILE G 431 -12.700 44.155 -10.157 1.00 10.76 C
ATOM 2798 CB ILE G 431 -13.777 43.106 -9.812 1.00 10.43 C
ATOM 2799 CGI ILE G 431 -13.615 42.625 -8.368 1.00 10.95 C
ATOM 2800 CD1 ILE G 431 -14.920 42.259 -7.695 1.00 12.08 C
ATOM 2801 CG2 ILE G 431 -13.720 41.940 -10.785 1.00 10.07 C
ATOM 2802 C ILE G 431 -12.770 44.465 -11.651 1.00 10.68 C
ATOM 2803 O ILE G 431 -13.790 44.954 -12.136 1.00 10.40 O
ATOM 2804 N ILE G 432 -11.677 44.225 -12.373 1.00 10.90 N
ATOM 2805 CA ILE G 432 -11.658 44.482 -13.815 1.00 11.42 C
ATOM 2806 CB ILE G 432 -10.276 44.936 -14.327 1.00 11.63 C
ATOM 2807 CGI ILE G 432 -9.411 45.460 -13.180 1.00 12.68 C
ATOM 2808 CD 1 ILE G 432 -7.977 45.738 -13.579 1.00 13.89 C
ATOM 2809 CG2 ILE G 432 -10.432 45.992 -15.412 1.00 12.24 C
ATOM 2810 C ILE G 432 -12.118 43.290 -14.648 1.00 11.41 C
ATOM 2811 O ILE G 432 -12.834 43.463 -15.635 1.00 11.63 O
ATOM 2812 N LYS G 433 -11.505 42.136 -14.405 1.00 11.52 N
ATOM 2813 CA LYS G 433 -11.792 40.950 -15.203 1.00 11.96 C
ATOM 2814 CB LYS G 433 -10.516 40.392 -15.837 1.00 12.31 C
ATOM 2815 CG LYS G 433 -10.770 39.317 -16.885 1.00 14.42 C
ATOM 2816 CD LYS G 433 -9.723 39.348 -17.987 1.00 16.74 C
ATOM 2817 CE LYS G 433 -9.997 38.283 -19.038 1.00 17.08 C
ATOM 2818 NZ LYS G 433 -9.612 38.735 -20.404 1.00 17.30 N
ATOM 2819 C LYS G 433 -12.496 39.873 -14.387 1.00 11.65 C
ATOM 2820 O LYS G 433 -12.479 39.899 -13.156 1.00 11.48 O
ATOM 2821 N TH G 434 -13.143 38.946 -15.086 1.00 11.28 N
ATOM 2822 CA THR G 434 -13.816 37.821 -14.445 1.00 11.21 C
ATOM 2823 CB THR G 434 -15.222 38.216 -13.955 1.00 11.30 C
ATOM 2824 OG1 THR G 434 -15.963 37.037 -13.619 1.00 11.83 O
ATOM 2825 CG2 THR G 434 -15.966 38.988 -15.035 1.00 11.84 C
ATOM 2826 C THR G 434 -13.939 36.646 -15.415 1.00 10.94 C
ATOM 2827 O THR G 434 -14.257 36.836 -16.589 1.00 10.93 O
ATOM 2828 N PHE G 435 -13.628 35.442 -14.939 1.00 11.10 N
ATOM 2829 CA PHE G 435 -12.871 34.486 -15.744 1.00 11.96 C
ATOM 2830 CB PHE G 435 -11.673 33.929 -14.977 1.00 11.51 C
ATOM 2831 CG PHE G 435 -10.437 34.772 -15.100 1.00 11.19 C
ATOM 2832 CD1 PHE G 435 -9.910 35.409 -13.989 1.00 10.86 C
ATOM 2833 CE1 PHE G 435 -8.824 36.254 -14.107 1.00 10.24 C
ATOM 2834 CZ PHE G 435 -8.286 36.516 -15.352 1.00 9.89 C
ATOM 2835 CE2 PHE G 435 -8.834 35.927 -16.474 1.00 10.78 C
ATOM 2836 CD2 PHE G 435 -9.920 35.082 -16.348 1.00 11.14 C
ATOM 2837 C PHE G 435 -13.678 33.371 -16.403 1.00 13.00 C
ATOM 2838 O PHE G 435 -14.218 32.494 -15.726 1.00 13.03 O
ATOM 2839 N SER G 436 -13.506 33.272 -17.717 1.00 13.89 N
ATOM 2840 CA SER G 436 -14.276 32.356 -18.546 1.00 14.67 C
ATOM 2841 CB SER G 436 -14.391 32.910 -19.969 1.00 15.04 C
ATOM 2842 OG SER G 436 -15.702 33.377 -20.235 1.00 16.58 O
ATOM 2843 C SER G 436 -13.627 30.975 -18.578 1.00 14.75 C
ATOM 2844 O SER G 436 -13.081 30.559 -19.601 1.00 14.75 O
ATOM 2845 N ASN G 437 -13.713 30.256 -17.465 1.00 14.44 N
ATOM 2846 CA ASN G 437 -13.595 28.805 -17.496 1.00 14.35 C
ATOM 2847 CB ASN G 437 -14.935 28.179 -17.896 1.00 14.75 C
ATOM 2848 CG ASN G 437 -14.999 26.690 -17.610 1.00 15.51 C
ATOM 2849 OD1 ASN G 437 -15.013 26.275 -16.450 1.00 16.85 O
ATOM 2850 ND2 ASN G 437 -15.246 25.906 -18.652 1.00 16.10 N
ATOM 2851 C ASN G 437 -12.497 28.371 -18.464 1.00 13.69 C
ATOM 2852 O ASN G 437 -12.754 27.652 -19.430 1.00 13.40 O
ATOM 2853 N GLY G 438 -11.290 28.880 -18.237 1.00 13.39 N
ATOM 2854 CA GLY G 438 -10.183 28.701 -19.170 1.00 12.92 C
ATOM 2855 C GLY G 438 -8.839 28.941 -18.510 1.00 12.72 C
ATOM 2856 O GLY G 438 -8.620 28.538 -17.367 1.00 12.83 O ATOM 2857 N CYS G 439 -7.971 29.677 -19.195 1.00 12.17 N
ATOM 2858 CA CYS G 439 -6.654 29.999 -18.658 1.00 11.52 C
ATOM 2859 CB CYS G 439 -5.696 28.822 -18.844 1.00 11.68 C
ATOM 2860 SG CYS G 439 -3.974 29.301 -19.104 1.00 12.89 S
ATOM 2861 C CYS G 439 -6.077 31.258 -19.297 1.00 10.95 C
ATOM 2862 O CYS G 439 -5.762 31.275 -20.488 1.00 10.77 O
ATOM 2863 N ASP G 440 -5.921 32.303 -18.490 1.00 10.41 N
ATOM 2864 CA ASP G 440 -5.546 33.619 -18.993 1.00 10.06 C
ATOM 2865 CB ASP G 440 -6.685 34.620 -18.778 1.00 10.85 C
ATOM 2866 CG ASP G 440 -7.418 34.956 -20.062 1.00 13.11 C
ATOM 2867 OD1 ASP G 440 -6.891 35.765 -20.854 1.00 14.97 O
ATOM 2868 OD2 ASP G 440 -8.559 34.479 -20.237 1.00 15.27 O
ATOM 2869 C ASP G 440 -4.276 34.131 -18.318 1.00 9.01 C
ATOM 2870 O ASP G 440 -3.793 33.542 -17.350 1.00 9.09 O
ATOM 2871 N TY G 441 -3.806 35.287 -18.778 1.00 7.92 N
ATOM 2872 CA TYR G 441 -2.645 35.959 -18.199 1.00 7.24 C
ATOM 2873 CB TYR G 441 -1.457 35.871 -19.165 1.00 7.04 C
ATOM 2874 CG TYR G 441 -0.227 36.631 -18.724 1.00 6.77 C
ATOM 2875 CD1 TYR G 441 0.762 36.008 -17.974 1.00 7.41 C
ATOM 2876 CE1 TYR G 441 1.902 36.688 -17.593 1.00 6.79 C
ATOM 2877 CZ TYR G 441 2.106 37.980 -18.034 1.00 6.49 C
ATOM 2878 OH TYR G 441 3.230 38.670 -17.635 1.00 5.09 O
ATOM 2879 CE2 TYR G 441 1.157 38.606 -18.817 1.00 7.52 C
ATOM 2880 CD2 TYR G 441 0.017 37.918 -19.186 1.00 7.12 C
ATOM 2881 C TYR G 441 -3.005 37.421 -17.946 1.00 6.89 C
ATOM 2882 O TYR G 441 -3.809 38.000 -18.677 1.00 7.12 O
ATOM 2883 N VAL G 442 -2.452 37.999 -16.886 1.00 6.73 N
ATOM 2884 CA VAL G 442 -2.612 39.427 -16.615 1.00 6.78 C
ATOM 2885 CB VAL G 442 -3.614 39.671 -15.472 1.00 6.51 C
ATOM 2886 CGI VAL G 442 -5.041 39.483 -15.967 1.00 7.38 C
ATOM 2887 CG2 VAL G 442 -3.322 38.742 -14.303 1.00 6.00 C
ATOM 2888 C VAL G 442 -1.262 40.025 -16.234 1.00 7.13 C
ATOM 2889 O VAL G 442 -0.272 39.301 -16.134 1.00 7.77 O
ATOM 2890 N SER G 443 -1.210 41.335 -16.022 1.00 7.12 N
ATOM 2891 CA SER G 443 0.062 41.970 -15.700 1.00 7.64 C
ATOM 2892 CB SER G 443 0.770 42.447 -16.969 1.00 7.83 C
ATOM 2893 OG SER G 443 0.637 43.847 -17.131 1.00 7.99 O
ATOM 2894 C SER G 443 -0.051 43.104 -14.690 1.00 8.16 C
ATOM 2895 O SER G 443 -1.142 43.607 -14.420 1.00 8.69 O
ATOM 2896 N ASN G 444 1.086 43.484 -14.117 1.00 8.73 N
ATOM 2897 CA ASN G 444 1.139 44.600 -13.184 1.00 9.50 C
ATOM 2898 CB ASN G 444 2.521 44.684 -12.538 1.00 9.65 C
ATOM 2899 CG ASN G 444 3.256 43.357 -12.565 1.00 10.64 C
ATOM 2900 OD1 ASN G 444 2.641 42.291 -12.498 1.00 12.28 O
ATOM 2901 ND2 ASN G 444 4.578 43.416 -12.685 1.00 11.75 N
ATOM 2902 C ASN G 444 0.791 45.922 -13.857 1.00 10.24 C
ATOM 2903 O ASN G 444 1.086 46.126 -15.034 1.00 9.89 O
ATOM 2904 N LYS G 445 0.266 46.855 -13.069 1.00 11.63 N
ATOM 2905 CA LYS G 445 -0.752 47.787 -13.545 1.00 13.07 C
ATOM 2906 CB LYS G 445 -0.107 49.048 -14.123 1.00 13.70 C
ATOM 2907 CG LYS G 445 -1.068 50.216 -14.307 1.00 15.80 C
ATOM 2908 CD LYS G 445 -2.384 49.986 -13.575 1.00 18.31 C
ATOM 2909 CE LYS G 445 -2.166 49.766 -12.086 1.00 19.03 C
ATOM 2910 NZ LYS G 445 -1.048 50.592 -11.554 1.00 20.02 N
ATOM 2911 C LYS G 445 -1.681 47.147 -14.572 1.00 12.96 C
ATOM 2912 O LYS G 445 -1.258 46.313 -15.372 1.00 13.24 O
ATOM 2913 N GLY G 446 -2.943 47.559 -14.558 1.00 13.08 N
ATOM 2914 CA GLY G 446 -4.051 46.616 -14.597 1.00 12.42 C
ATOM 2915 C GLY G 446 -4.212 45.900 -13.272 1.00 11.83 C
ATOM 2916 O GLY G 446 -4.832 46.426 -12.347 1.00 12.44 O ATOM 2917 N VAL G 447 -3.517 44.777 -13.126 1.00 10.63 N
ATOM 2918 CA VAL G 447 -3.875 43.795 -12.114 1.00 10.01 C
ATOM 2919 CB VAL G 447 -3.898 42.365 -12.681 1.00 9.97 C
ATOM 2920 CGI VAL G 447 -4.591 41.422 -11.708 1.00 10.51 C
ATOM 2921 CG2 VAL G 447 -4.594 42.345 -14.033 1.00 10.50 C
ATOM 2922 C VAL G 447 -2.978 43.851 -10.882 1.00 9.53 C
ATOM 2923 O VAL G 447 -1.761 44.008 -10.985 1.00 9.61 O
ATOM 2924 N ASP G 448 -3.586 43.575 -9.735 1.00 9.16 N
ATOM 2925 CA ASP G 448 -2.956 43.763 -8.437 1.00 8.75 C
ATOM 2926 CB ASP G 448 -3.515 45.022 -7.771 1.00 9.22 C
ATOM 2927 CG ASP G 448 -2.579 45.599 -6.729 1.00 11.44 C
ATOM 2928 ODl ASP G 448 -1.725 44.849 -6.212 1.00 13.83 O
ATOM 2929 OD2 ASP G 448 -2.713 46.799 -6.409 1.00 14.13 O
ATOM 2930 C ASP G 448 -3.313 42.546 -7.598 1.00 8.18 C
ATOM 2931 O ASP G 448 -2.555 42.122 -6.725 1.00 8.06 O
ATOM 2932 N TH G 449 -4.451 41.949 -7.933 1.00 7.63 N
ATOM 2933 CA THR G 449 -4.991 40.823 -7.192 1.00 6.80 C
ATOM 2934 CB THR G 449 -5.988 41.293 -6.116 1.00 6.89 C
ATOM 2935 OG1 THR G 449 -5.284 41.584 -4.902 1.00 6.16 O
ATOM 2936 CG2 THR G 449 -7.032 40.219 -5.848 1.00 7.55 C
ATOM 2937 C THR G 449 -5.717 39.906 -8.164 1.00 6.53 C
ATOM 2938 O THR G 449 -6.385 40.370 -9.087 1.00 6.59 O
ATOM 2939 N VAL G 450 -5.536 38.603 -7.989 1.00 6.07 N
ATOM 2940 CA VAL G 450 -6.531 37.646 -8.434 1.00 6.02 C
ATOM 2941 CB VAL G 450 -5.981 36.723 -9.535 1.00 5.61 C
ATOM 2942 CGI VAL G 450 -5.377 37.545 -10.663 1.00 5.32 C
ATOM 2943 CG2 VAL G 450 -4.954 35.761 -8.958 1.00 5.55 C
ATOM 2944 C VAL G 450 -7.021 36.811 -7.263 1.00 6.37 C
ATOM 2945 O VAL G 450 -6.299 36.609 -6.287 1.00 6.54 O
ATOM 2946 N SER G 451 -8.307 36.486 -7.288 1.00 6.41 N
ATOM 2947 CA SER G 451 -8.857 35.507 -6.370 1.00 6.70 C
ATOM 2948 CB SER G 451 -9.995 36.120 -5.553 1.00 7.13 C
ATOM 2949 OG SER G 451 -10.537 37.254 -6.207 1.00 9.26 O
ATOM 2950 C SER G 451 -9.354 34.292 -7.139 1.00 6.47 C
ATOM 2951 O SER G 451 -9.896 34.423 -8.238 1.00 6.54 O
ATOM 2952 N VAL G 452 -8.962 33.116 -6.664 1.00 6.56 N
ATOM 2953 CA VAL G 452 -9.578 31.868 -7.091 1.00 6.31 C
ATOM 2954 CB VAL G 452 -8.516 30.849 -7.542 1.00 5.74 C
ATOM 2955 CGI VAL G 452 -9.170 29.688 -8.275 1.00 5.06 C
ATOM 2956 CG2 VAL G 452 -7.471 31.523 -8.419 1.00 5.56 C
ATOM 2957 C VAL G 452 -10.381 31.264 -5.944 1.00 6.60 C
ATOM 2958 O VAL G 452 -9.861 31.079 -4.844 1.00 7.04 O
ATOM 2959 N GLY G 453 -11.652 30.975 -6.198 1.00 6.54 N
ATOM 2960 CA GLY G 453 -12.581 30.650 -5.124 1.00 6.43 C
ATOM 2961 C GLY G 453 -12.375 31.548 -3.920 1.00 6.09 C
ATOM 2962 O GLY G 453 -12.581 32.759 -3.999 1.00 5.90 O
ATOM 2963 N ASN G 454 -11.872 30.971 -2.833 1.00 6.02 N
ATOM 2964 CA ASN G 454 -11.672 31.727 -1.603 1.00 6.39 C
ATOM 2965 CB ASN G 454 -12.335 31.027 -0.420 1.00 6.81 C
ATOM 2966 CG ASN G 454 -13.717 31.567 -0.135 1.00 8.99 C
ATOM 2967 OD1 ASN G 454 -13.867 32.523 0.625 1.00 11.67 O
ATOM 2968 ND2 ASN G 454 -14.693 31.112 -0.911 1.00 10.25 N
ATOM 2969 C ASN G 454 -10.211 32.020 -1.296 1.00 6.15 C
ATOM 2970 O ASN G 454 -9.900 32.765 -0.367 1.00 6.47 O
ATOM 2971 N THR G 455 -9.322 31.491 -2.128 1.00 5.40 N
ATOM 2972 CA THR G 455 -7.912 31.841 -2.053 1.00 4.53 C
ATOM 2973 CB THR G 455 -7.033 30.774 -2.724 1.00 4.70 C
ATOM 2974 OG1 THR G 455 -7.344 29.486 -2.180 1.00 5.28 O
ATOM 2975 CG2 THR G 455 -5.560 31.074 -2.491 1.00 5.57 C
ATOM 2976 C THR G 455 -7.659 33.187 -2.717 1.00 4.01 C ATOM 2977 O TH G 455 -8.312 33.540■ -3.698 1.00 3.78 O
ATOM 2978 N LEU G 456 -6.716 33.943 - 2.165 1.00 3.87 N
ATOM 2979 CA LEU G 456 -6.355 35.237 -2.726 1.00 4.05 C
ATOM 2980 CB LEU G 456 -6.684 36.360 -1.742 1.00 3.95 C
ATOM 2981 CG LEU G 456 -6.595 37.779 -2.306 1.00 3.76 c
ATOM 2982 CD1 LEU G 456 -7.572 37.962 -3.457 1.00 5.35 c
ATOM 2983 CD2 LEU G 456 -6.845 38.809 -1.216 1.00 4.10 c
ATOM 2984 C LEU G 456 -4.879 35.288 - 3.105 1.00 4.47 c
ATOM 2985 O LEU G 456 -4.006 35.028 - 2.276 1.00 4.94 o
ATOM 2986 N TYR G 457 -4.609 35.652■ -4.355 1.00 4.59 N
ATOM 2987 CA TYR G 457 -3.242 35.786 -4.849 1.00 4.60 c
ATOM 2988 CB TYR G 457 -3.056 34.938 -6.113 1.00 4.71 c
ATOM 2989 CG TYR G 457 -3.201 33.447 -5.888 1.00 5.62 c
ATOM 2990 CD1 TYR G 457 -4.451 32.838 -5.896 1.00 7.09 c
ATOM 2991 CE1 TYR G 457 -4.582 31.473 -5.712 1.00 8.22 c
ATOM 2992 CZ TYR G 457 -3.456 30.699 -5.533 1.00 8.06 c
ATOM 2993 OH TYR G 457 -3.580 29.341 -5.349 1.00 8.80 o
ATOM 2994 CE2 TYR G 457 -2.204 31.276 -5.547 1.00 7.18 c
ATOM 2995 CD2 TYR G 457 -2.083 32.639 -5.735 1.00 6.66 c
ATOM 2996 C TYR G 457 -2.924 37.256 - 5.152 1.00 4.46 c
ATOM 2997 O TYR G 457 -3.742 37.959 ■ -5.745 1.00 4.92 o
ATOM 2998 N TYR G 458 -1.727 37.706■ -4.772 1.00 3.90 N
ATOM 2999 CA TYR G 458 -1.312 39.118 -4.919 1.00 3.26 c
ATOM 3000 CB TYR G 458 -0.740 39.635 -3.582 1.00 3.16 c
ATOM 3001 CG TYR G 458 -1.716 39.659 -2.411 1.00 3.29 c
ATOM 3002 CD1 TYR G 458 -1.782 38.602 -1.509 1.00 3.93 c
ATOM 3003 CE1 TYR G 458 -2.632 38.646 -0.412 1.00 4.90 c
ATOM 3004 CZ TYR G 458 -3.395 39.773 -0.185 1.00 5.12 c
ATOM 3005 OH TYR G 458 -4.250 39.817 0.893 1.00 5.42 o
ATOM 3006 CE2 TYR G 458 -3.311 40.852 -1.039 1.00 4.72 c
ATOM 3007 CD2 TYR G 458 -2.457 40.801 -2.128 1.00 3.89 c
ATOM 3008 C TYR G 458 -0.248 39.290 - 6.043 1.00 3.04 c
ATOM 3009 O TYR G 458 0.749 38.569 - 6.041 1.00 3.37 o
ATOM 3010 N VAL G 459 -0.351 40.348 -6.866 1.00 2.71 N
ATOM 3011 CA VAL G 459 0.376 40.435 -8.177 1.00 2.61 c
ATOM 3012 CB VAL G 459 -0.589 40.554 -9.380 1.00 2.22 c
ATOM 3013 CGI VAL G 459 0.154 40.287 -10.682 1.00 2.62 c
ATOM 3014 CG2 VAL G 459 -1.756 39.589 -9.224 1.00 2.61 c
ATOM 3015 C VAL G 459 1.609 41.392 - 8.360 1.00 3.03 c
ATOM 3016 O VAL G 459 2.575 41.281 - ■7.604 1.00 3.21 o
ATOM 3017 N ASN G 460 1.708 42.037 - 9.537 1.00106.93 N
ATOM 3018 CA ASN G 460 2.714 43.111 -9.870 1.00 95.54 c
ATOM 3019 CB ASN G 460 3.598 43.589 -8.700 1.00 20.00 c
ATOM 3020 CG ASN G 460 4.310 44.931 -9.000 1.00 20.00 c
ATOM 3021 OD1 ASN G 460 3.713 45.851 -9.563 1.00 20.00 o
ATOM 3022 ND2 ASN G 460 5.548 45.065 -8.532 1.00 20.00 N
ATOM 3023 C ASN G 460 3.403 43.322 -11.247 1.00 99.41 c
ATOM 3024 O ASN G 460 3.869 44.430 - 11.523 1.00108.91 o
ATOM 3025 N LYS G 461 3.568 42.271 -12.055 1.00 97.04 N
ATOM 3026 CA LYS G 461 4.464 42.327 - ■13.236 1.00105.93 c
ATOM 3027 CB LYS G 461 5.335 41.068 - 13.312 1.00 20.00 c
ATOM 3028 CG LYS G 461 6.382 40.951 - ■12.209 1.00 20.00 c
ATOM 3029 CD LYS G 461 7.131 39.623 - ■12.296 1.00 20.00 c
ATOM 3030 CE LYS G 461 8.255 39.536 - 11.268 1.00 20.00 c
ATOM 3031 NZ LYS G 461 8.886 38.184 - 11.223 1.00 20.00 N
ATOM 3032 C LYS G 461 3.727 42.546 -14.573 1.00102.28 c
ATOM 3033 O LYS G 461 2.507 42.702 -14.590 1.00105.02 o
ATOM 3034 N GLN G 462 4.464 42.556 - 15.685 1.00 96.68 N
ATOM 3035 CA GLN G 462 3.854 42.633 -17.020 1.00105.71 c
ATOM 3036 CB GLN G 462 3.988 44.047 -17.593 1.00 20.00 c ATOM 3037 CG GLN G 462 3.237 45.115 -16.814 1.00 20.00 C ATOM 3038 CD GLN G 462 3.484 46.512 -17.353 1.00 20.00 c ATOM 3039 OE1 GLN G 462 4.527 46.786 -17.947 1.00 20.00 o ATOM 3040 NE2 GLN G 462 2.529 47.408 -17.135 1.00 20.00 N ATOM 3041 C GLN G 462 4.479 41.626 -17.986 1.00101.50 c ATOM 3042 O GLN G 462 5.701 41.501 -18.051 1.00105.94 o ATOM 3043 N GLU G 463 3.646 40.946 -18.769 1.00 98.92 N ATOM 3044 CA GLU G 463 4.140 39.928 -19.693 1.00108.59 c ATOM 3045 CB GLU G 463 3.380 38.612 -19.512 1.00 20.00 c ATOM 3046 CG GLU G 463 3.682 37.900 -18.201 1.00 20.00 c ATOM 3047 CD GLU G 463 2.842 36.650 -18.005 1.00 20.00 c ATOM 3048 OE1 GLU G 463 2.003 36.350 -18.881 1.00 20.00 o ATOM 3049 OE2 GLU G 463 3.075 35.929 -17.011 1.00 20.00 o ATOM 3050 C GLU G 463 4.074 40.384 21.146 1.00116.39 c ATOM 3051 O GLU G 463 3.025 40.814 21.627 1.00118.70 o ATOM 3052 N GLY G 464 5.200 40.272 -21.845 1.00127.70 N ATOM 3053 CA GLY G 464 5.261 40.610 -23.261 1.00143.17 c ATOM 3054 C GLY G 464 4.710 39.509 -24.146 1.00149.77 c ATOM 3055 O GLY G 464 4.443 38.400 -23.681 1.00155.06 o ATOM 3056 N LYS G 465 4.544 39.816 -25.428 1.00153.73 N ATOM 3057 CA LYS G 465 3.994 38.862 -26.384 1.00153.69 c ATOM 3058 CB LYS G 465 4.816 37.571 -26.389 1.00 20.00 c ATOM 3059 CG LYS G 465 6.228 37.735 -26.927 1.00 20.00 c ATOM 3060 CD LYS G 465 6.996 36.424 -26.873 1.00 20.00 c ATOM 3061 CE LYS G 465 8.402 36.585 -27.426 1.00 20.00 c ATOM 3062 NZ LYS G 465 9.172 35.312 -27.363 1.00 20.00 N ATOM 3063 C LYS G 465 2.532 38.552 -26.080 1.00155.37 c ATOM 3064 O LYS G 465 1.710 38.437 -26.988 1.00155.20 o ATOM 3065 N GLU G 472 -0.074 35.733 -32.259 1.00145.47 N ATOM 3066 CA GLU G 472 -0.706 34.866 -33.247 1.00151.12 c ATOM 3067 CB GLU G 472 0.178 34.736 -34.490 1.00 20.00 c ATOM 3068 CG GLU G 472 0.339 36.028 -35.276 1.00 20.00 c ATOM 3069 CD GLU G 472 1.271 35.876 -36.463 1.00 20.00 c ATOM 3070 OE1 GLU G 472 1.954 34.835 -36.556 1.00 20.00 o ATOM 3071 OE2 GLU G 472 1.325 36.803 -37.299 1.00 20.00 o ATOM 3072 C GLU G 472 -0.993 33.486 -32.663 1.00153.35 c ATOM 3073 O GLU G 472 -0.069 32.755 -32.306 1.00159.41 o ATOM 3074 N PRO G 473 -2.282 33.131 -32.557 1.00150.51 N ATOM 3075 CA PRO G 473 -2.668 31.819 -32.081 1.00141.97 c ATOM 3076 CB PRO G 473 -3.684 32.152 -30.990 1.00 20.00 c ATOM 3077 CG PRO G 473 -4.311 33.467 -31.446 1.00 20.00 c ATOM 3078 CD PRO G 473 -3.423 34.059 -32.523 1.00 20.00 c ATOM 3079 C PRO G 473 -3.357 31.051 -33.200 1.00135.14 c ATOM 3080 O PRO G 473 -3.883 31.662 -34.131 1.00144.93 o ATOM 3081 N ILE G 474 -3.379 29.727 -33.098 1.00118.07 N ATOM 3082 CA ILE G 474 -3.969 28.899 -34.142 1.00105.14 c ATOM 3083 CB ILE G 474 -3.193 29.027 -35.469 1.00 20.00 c ATOM 3084 CGI ILE G 474 -3.315 30.446 -36.028 1.00 20.00 c ATOM 3085 CD1 ILE G 474 -2.352 30.745 -37.156 1.00 20.00 c ATOM 3086 CG2 ILE G 474 -3.696 28.008 -36.481 1.00 20.00 c ATOM 3087 C ILE G 474 -4.007 27.432 -33.730 1.00104.75 c ATOM 3088 O ILE G 474 -3.033 26.702 -33.915 1.00111.83 o ATOM 3089 N ILE G 475 -5.149 26.992 -33.213 1.00 94.65 N ATOM 3090 CA ILE G 475 -5.249 25.667 -32.611 1.00 79.88 c ATOM 3091 CB ILE G 475 -5.443 25.753 -31.087 1.00 20.00 c ATOM 3092 CGI ILE G 475 -4.165 26.260 -30.413 1.00 20.00 c ATOM 3093 CD1 ILE G 475 -4.414 27.012 -29.122 1.00 20.00 c ATOM 3094 CG2 ILE G 475 -5.873 24.406 -30.525 1.00 20.00 c ATOM 3095 C ILE G 475 -6.374 24.834 -33.223 1.00 79.52 c ATOM 3096 O ILE G 475 -7.554 25.117 -33.016 1.00 82.70 o ATOM 3097 N ASNG476 -5.99623.761 -33.912 1.0069.64 N
ATOM 3098 CA ASNG 476 -6.96222.821 -34.472 1.0068.88 C
ATOM 3099 CB ASNG476 -6.36522.100 -35.683 1.0020.00 C
ATOM 3100 CG ASNG 476 -6.17023.019 -36.872 1.0020.00 C
ATOM 3101 OD1 ASNG 476 -6.85524.032 -37.009 1.0020.00 O
ATOM 3102 ND2 ASNG 476 -5.251 22.651 -37.756 1.0020.00 N
ATOM 3103 C ASNG476 -7.43421.799 -33.443 1.0067.13 C
ATOM 3104 O ASNG 476 -6.62821.229 -32.707 1.0073.10 O
ATOM 3105 N PHEG477 -8.73521.527 -33.438 1.0064.95 N
ATOM 3106 CA PHEG477 -9.32720.624 -32.455 1.0068.13 C
ATOM 3107 CB PHEG477 -10.85420.711 -32.493 1.0020.00 C
ATOM 3108 CG PHEG477 -11.39722.047 -32.079 1.0020.00 C
ATOM 3109 CD1 PHEG 477 -11.58022.352-30.740 1.0020.00 C
ATOM 3110 CE1 PHEG 477 -12.08623.580 -30.357 1.0020.00 C
ATOM 3111 CZ PHEG 477 -12.42624.514-31.316 1.0020.00 C
ATOM 3112 CE2 PHEG 477 -12.257 24.219 -32.654 1.0020.00 C
ATOM 3113 CD2 PHEG 477 -11.75022.989 -33.030 1.0020.00 C
ATOM 3114 C PHEG 477 -8.890 19.180 -32.672 1.0065.57 C
ATOM 3115 O PHEG 477 -9.270 18.290 -31.911 1.0049.83 O
ATOM 3116 N TY G 478 -8.204 18.931 -33.782 1.0051.97 N
ATOM 3117 CA TYR G 478 -7.618 17.619 -34.036 1.0052.01 C
ATOM 3118 CB TYR G 478 -7.356 17.428 -35.530 1.0020.00 C
ATOM 3119 CG TYR G 478 -8.609 17.426 -36.372 1.0020.00 C
ATOM 3120 CD1 TYR G 478 -9.337 16.259 -36.567 1.0020.00 C
ATOM 3121 CE1TYRG478 -10.489 16.255 -37.329 1.0020.00 C
ATOM 3122 CZ TYR G 478 -10.930 17.429 -37.902 1.0020.00 C
ATOM 3123 OH TYR G 478 -12.078 17.432 -38.658 1.0020.00 O
ATOM 3124 CE2TYRG478 -10.230 18.602 -37.717 1.0020.00 C
ATOM 3125 CD2TYRG478 -9.079 18.596 -36.954 1.0020.00 C
ATOM 3126 C TYR G 478 -6.325 17.459 -33.251 1.0066.63 C
ATOM 3127 O TYR G 478 -5.548 16.535 -33.492 1.0063.45 O
ATOM 3128 N ASP G 479 -6.062 18.423 -32.375 1.0065.34 N
ATOM 3129 CA ASP G 479 -4.928 18.351 -31.469 1.0065.32 C
ATOM 3130 CB ASP G 479 -4.205 19.698 -31.413 1.0020.00 C
ATOM 3131 CG ASP G 479 -3.50920.038 -32.717 1.0020.00 C
ATOM 3132 OD1ASPG479 -3.293 19.119 -33.534 1.0020.00 O
ATOM 3133 OD2 ASP G 479 -3.18421.225 -32.930 1.0020.00 O
ATOM 3134 C ASP G 479 -5.383 17.937 -30.076 1.0064.83 C
ATOM 3135 O ASP G 479 -4.561 17.574-29.236 1.0060.42 O
ATOM 3136 N PROG480 -6.707 17.893 -29.861 1.0047.60 N
ATOM 3137 CA PROG480 -7.262 17.523 -28.572 1.0046.52 C
ATOM 3138 CB PROG480 -8.509 18.400 -28.480 1.0020.00 C
ATOM 3139 CG PROG480 -8.954 18.565 -29.904 1.0020.00 C
ATOM 3140 CD PROG480 -7.755 18.332 -30.799 1.0020.00 C
ATOM 3141 C PROG 480 -7.662 16.056 -28.548 1.0052.36 C
ATOM 3142 O PROG480 -8.804 15.721 -28.860 1.0064.15 O
ATOM 3143 N LEU G 481 -6.698 15.183 -28.281 1.0062.90 N
ATOM 3144 CA LEU G 481 -6.977 13.759 -28.138 1.0054.24 C
ATOM 3145 CB LEU G 481 -6.143 12.944 -29.128 1.0020.00 C
ATOM 3146 CG LEU G 481 -6.449 13.142-30.613 1.0020.00 C
ATOM 3147 CD1LEUG481 -5.475 12.348 -31.471 1.0020.00 C
ATOM 3148 CD2LEUG481 -7.884 12.747 -30.922 1.0020.00 C
ATOM 3149 C LEU G 481 -6.700 13.285 -26.717 1.0059.81 C
ATOM 3150 O LEU G 481 -6.199 14.041 -25.884 1.0064.98 O
ATOM 3151 N VALG482 -6.956 12.008 -26.470 1.0059.66 N
ATOM 3152 CA VALG482 -6.588 11.404-25.203 1.0049.67 C
ATOM 3153 CB VAL G 482 -7.741 10.579 -24.619 1.0020.00 C
ATOM 3154 CGI VAL G 482 -7.390 10.116 -23.220 1.0020.00 C
ATOM 3155 CG2 VAL G 482 -9.021 11.398 -24.607 1.0020.00 C
ATOM 3156 C VAL G 482 -5.357 10.525 -25.372 1.0053.03 C ATOM 3157 O VAL G 482 -5.147 9.945 -26.437 1.00 46.27 O
ATOM 3158 N PHE G 483 -4.464 10.579 -24.387 1.00 61.61 N
ATOM 3159 CA PHE G 483 -3.282 9.723 -24.370 1.00 65.03 C
ATOM 3160 CB PHE G 483 -2.011 10.562 -24.235 1.00 20.00 C
ATOM 3161 CG PHE G 483 -1.788 11.500 -25.385 1.00 20.00 C
ATOM 3162 CD1 PHE G 483 -1.173 11.059 -26.546 1.00 20.00 C
ATOM 3163 CE1 PHE G 483 -1.039 11.897 -27.632 1.00 20.00 C
ATOM 3164 CZ PHE G 483 -1.577 13.170 -27.589 1.00 20.00 C
ATOM 3165 CE2 PHE G 483 -2.199 13.618 -26.442 1.00 20.00 C
ATOM 3166 CD2 PHE G 483 -2.315 12.781 -25.355 1.00 20.00 C
ATOM 3167 C PHE G 483 -3.358 8.663 -23.275 1.00 71.00 C
ATOM 3168 O PHE G 483 -2.688 8.776 -22.248 1.00100.44 O
ATOM 3169 N PRO G 484 -4.338 7.759 -23.403 1.00 54.44 N
ATOM 3170 CA PRO G 484 -4.502 6.677 -22.459 1.00 47.46 C
ATOM 3171 CB PRO G 484 -5.761 7.096 -21.701 1.00 20.00 C
ATOM 3172 CG PRO G 484 -6.554 7.922 -22.714 1.00 20.00 C
ATOM 3173 CD PRO G 484 -5.649 8.206 -23.894 1.00 20.00 C
ATOM 3174 C PRO G 484 -4.778 5.378 -23.204 1.00 41.56 C
ATOM 3175 O PRO G 484 -5.689 5.321 -24.029 1.00 46.53 O
ATOM 3176 N SER G 485 -3.961 4.363 -22.958 1.00 46.30 N
ATOM 3177 CA SER G 485 -4.081 3.108 -23.686 1.00 49.30 C
ATOM 3178 CB SER G 485 -3.559 1.943 -22.841 1.00 20.00 C
ATOM 3179 OG SER G 485 -4.215 1.884 -21.588 1.00 20.00 O
ATOM 3180 C SER G 485 -5.521 2.856 -24.147 1.00 41.24 C
ATOM 3181 O SER G 485 -5.809 2.890 -25.345 1.00 46.93 O
ATOM 3182 N ASP G 486 -6.437 2.720 -23.190 1.00 49.48 N
ATOM 3183 CA ASP G 486 -7.816 2.321 -23.485 1.00 37.44 C
ATOM 3184 CB ASP G 486 -8.659 2.287 -22.205 1.00 20.00 C
ATOM 3185 CG ASP G 486 -8.296 1.125 -21.289 1.00 20.00 C
ATOM 3186 OD1 ASP G 486 -7.611 0.188 -21.746 1.00 20.00 O
ATOM 3187 OD2 ASP G 486 -8.637 1.184 -20.089 1.00 20.00 O
ATOM 3188 C ASP G 486 -8.447 3.271 -24.491 1.00 45.66 C
ATOM 3189 O ASP G 486 -9.005 2.844 -25.501 1.00 39.86 O
ATOM 3190 N GLU G 487 -8.317 4.566 -24.225 1.00 49.20 N
ATOM 3191 CA GLU G 487 -8.853 5.585 -25.116 1.00 45.70 C
ATOM 3192 CB GLU G 487 -8.656 6.982 -24.525 1.00 20.00 C
ATOM 3193 CG GLU G 487 -9.449 7.237 -23.251 1.00 20.00 C
ATOM 3194 CD GLU G 487 -9.144 8.590 -22.635 1.00 20.00 C
ATOM 3195 OE1 GLU G 487 -8.175 9.245 -23.078 1.00 20.00 O
ATOM 3196 OE2 GLU G 487 -9.865 8.988 -21.695 1.00 20.00 O
ATOM 3197 C GLU G 487 -8.222 5.504 -26.501 1.00 41.48 C
ATOM 3198 O GLU G 487 -8.914 5.623 -27.512 1.00 48.92 O
ATOM 3199 N PHE G 488 -6.910 5.306 -26.545 1.00 42.16 N
ATOM 3200 CA PHE G 488 -6.206 5.215 -27.815 1.00 39.33 C
ATOM 3201 CB PHE G 488 -4.701 5.086 -27.590 1.00 20.00 C
ATOM 3202 CG PHE G 488 -4.074 6.308 -26.992 1.00 20.00 C
ATOM 3203 CD 1 PHE G 488 -3.910 7.454 -27.747 1.00 20.00 C
ATOM 3204 CE1 PHE G 488 -3.320 8.574 -27.202 1.00 20.00 C
ATOM 3205 CZ PHE G 488 -2.847 8.542 -25.898 1.00 20.00 C
ATOM 3206 CE2 PHE G 488 -3.006 7.404 -25.136 1.00 20.00 C
ATOM 3207 CD2 PHE G 488 -3.630 6.302 -25.678 1.00 20.00 C
ATOM 3208 C PHE G 488 -6.724 4.040 -28.634 1.00 43.06 C
ATOM 3209 O PHE G 488 -7.101 4.203 -29.794 1.00 61.71 O
ATOM 3210 N ASP G 489 -6.910 2.906 -27.972 1.00 41.95 N
ATOM 3211 CA ASP G 489 -7.330 1.695 -28.658 1.00 42.75 C
ATOM 3212 CB ASP G 489 -7.257 0.499 -27.717 1.00 20.00 C
ATOM 3213 CG ASP G 489 -5.838 0.116 -27.389 1.00 20.00 C
ATOM 3214 OD1 ASP G 489 -4.920 0.637 -28.056 1.00 20.00 O
ATOM 3215 OD2 ASP G 489 -5.636 -0.633 -26.411 1.00 20.00 O
ATOM 3216 C ASP G 489 -8.733 1.825 -29.233 1.00 45.61 C ATOM 3217 O ASP G 489 -9.066 1.181 -30.226 1.00 54.39 O
ATOM 3218 N ALA G 490 -9.568 2.622 -28.575 1.00 42.89 N
ATOM 3219 CA ALA G 490 -10.929 2.848 -29.044 1.00 38.40 C
ATOM 3220 CB ALA G 490 -11.760 3.516 -27.963 1.00 20.00 C
ATOM 3221 C ALA G 490 -10.932 3.687 -30.315 1.00 39.67 C
ATOM 3222 O ALA G 490 -11.651 3.386 -31.267 1.00 56.80 O
ATOM 3223 N SE G 491 -10.138 4.752 -30.315 1.00 40.38 N
ATOM 3224 CA SER G 491 -9.984 5.586 -31.499 1.00 41.77 C
ATOM 3225 CB SER G 491 -9.155 6.831 -31.176 1.00 20.00 C
ATOM 3226 OG SER G 491 -7.806 6.490 -30.912 1.00 20.00 O
ATOM 3227 C SER G 491 -9.333 4.801 -32.631 1.00 39.01 C
ATOM 3228 O SER G 491 -9.688 4.967 -33.798 1.00 36.91 O
ATOM 3229 N ILE G 492 -8.387 3.938 -32.278 1.00 38.11 N
ATOM 3230 CA ILE G 492 -7.741 3.077 -33.259 1.00 41.21 C
ATOM 3231 CB ILE G 492 -6.630 2.211 -32.620 1.00 20.00 C
ATOM 3232 CGI ILE G 492 -5.507 3.092 -32.061 1.00 20.00 C
ATOM 3233 CD 1 ILE G 492 -4.533 2.346 -31.163 1.00 20.00 C
ATOM 3234 CG2 ILE G 492 -6.067 1.219 -33.634 1.00 20.00 C
ATOM 3235 C ILE G 492 -8.773 2.170 -33.916 1.00 39.22 C
ATOM 3236 O ILE G 492 -8.778 2.008 -35.135 1.00 47.54 O
ATOM 3237 N SER G 493 -9.703 1.662 -33.111 1.00 41.64 N
ATOM 3238 CA SER G 493 -10.786 0.819 -33.612 1.00 35.15 C
ATOM 3239 CB SER G 493 -11.579 0.202 -32.454 1.00 20.00 C
ATOM 3240 OG SER G 493 -12.267 1.196 -31.716 1.00 20.00 O
ATOM 3241 C SER G 493 -11.716 1.614 -34.523 1.00 47.90 C
ATOM 3242 O SER G 493 -12.169 1.115 -35.555 1.00 50.94 O
ATOM 3243 N GLN G 494 -11.936 2.877 -34.169 1.00 42.51 N
ATOM 3244 CA GLN G 494 -12.789 3.766 -34.955 1.00 41.96 C
ATOM 3245 CB GLN G 494 -13.107 5.036 -34.167 1.00 20.00 C
ATOM 3246 CG GLN G 494 -13.991 4.813 -32.955 1.00 20.00 C
ATOM 3247 CD GLN G 494 -14.211 6.084 -32.163 1.00 20.00 C
ATOM 3248 OE1 GLN G 494 -13.406 7.013 -32.223 1.00 20.00 O
ATOM 3249 NE2 GLN G 494 -15.317 6.140 -31.430 1.00 20.00 N
ATOM 3250 C GLN G 494 -12.151 4.137 -36.291 1.00 33.86 C
ATOM 3251 O GLN G 494 -12.829 4.195 -37.318 1.00 54.89 O
ATOM 3252 N VAL G 495 -10.881 4.523 -36.241 1.00 34.99 N
ATOM 3253 CA VAL G 495 -10.108 4.772 -37.451 1.00 38.42 C
ATOM 3254 CB VAL G 495 -8.642 5.097 -37.120 1.00 20.00 C
ATOM 3255 CGI VAL G 495 -7.840 5.297 -38.394 1.00 20.00 C
ATOM 3256 CG2 VAL G 495 -8.562 6.327 -36.231 1.00 20.00 C
ATOM 3257 C VAL G 495 -10.152 3.573 -38.393 1.00 42.74 C
ATOM 3258 O VAL G 495 -10.424 3.720 -39.584 1.00 44.00 O
ATOM 3259 N ASN G 496 -9.947 2.383 -37.838 1.00 42.45 N
ATOM 3260 CA ASN G 496 -9.967 1.147 -38.617 1.00 43.01 C
ATOM 3261 CB ASN G 496 -9.572 -0.046 -37.743 1.00 20.00 C
ATOM 3262 CG ASN G 496 -8.118 0.000 -37.319 1.00 20.00 C
ATOM 3263 OD1 ASN G 496 -7.293 0.648 -37.965 1.00 20.00 O
ATOM 3264 ND2 ASN G 496 -7.796 -0.684 -36.226 1.00 20.00 N
ATOM 3265 C ASN G 496 -11.305 0.875 -39.310 1.00 43.13 C
ATOM 3266 O ASN G 496 -11.334 0.405 -40.448 1.00 54.76 O
ATOM 3267 N GLU G 497 -12.407 1.099 -38.598 1.00 42.08 N
ATOM 3268 CA GLU G 497 -13.738 0.938 -39.183 1.00 43.13 C
ATOM 3269 CB GLU G 497 -14.827 1.144 -38.127 1.00 20.00 C
ATOM 3270 CG GLU G 497 -14.937 0.018 -37.110 1.00 20.00 C
ATOM 3271 CD GLU G 497 -15.946 0.316 -36.017 1.00 20.00 C
ATOM 3272 OE1 GLU G 497 -16.552 1.408 -36.049 1.00 20.00 O
ATOM 3273 OE2 GLU G 497 -16.177 -0.566 -35.164 1.00 20.00 O
ATOM 3274 C GLU G 497 -13.937 1.915 -40.337 1.00 49.77 C
ATOM 3275 O GLU G 497 -14.552 1.580 -41.349 1.00 42.88 O
ATOM 3276 N LYS G 498 -13.367 3.108 -40.195 1.00 41.82 N ATOM 3277 CA LYS G 498 -13.435 4.123 -41.240 1.00 53.60 C
ATOM 3278 CB LYS G 498 -12.968 5.479 -40.705 1.00 20.00 C
ATOM 3279 CG LYS G 498 -13.937 6.125 -39.728 1.00 20.00 C
ATOM 3280 CD LYS G 498 -13.439 7.484 -39.269 1.00 20.00 C
ATOM 3281 CE LYS G 498 -14.393 8.108 -38.265 1.00 20.00 C
ATOM 3282 NZ LYS G 498 -13.896 9.421 -37.768 1.00 20.00 N
ATOM 3283 C LYS G 498 -12.611 3.724 -42.458 1.00 55.29 C
ATOM 3284 O LYS G 498 -13.033 3.926 -43.594 1.00 61.06 O
ATOM 3285 N ILE G 499 -11.430 3.165 -42.214 1.00 52.22 N
ATOM 3286 CA ILE G 499 -10.609 2.604 -43.284 1.00 48.26 C
ATOM 3287 CB ILE G 499 -9.296 2.009 -42.729 1.00 20.00 C
ATOM 3288 CGI ILE G 499 -8.446 3.101 -42.072 1.00 20.00 C
ATOM 3289 CD 1 ILE G 499 -7.506 2.582 -41.002 1.00 20.00 C
ATOM 3290 CG2 ILE G 499 -8.516 1.288 -43.825 1.00 20.00 C
ATOM 3291 C ILE G 499 -11.376 1.515 -44.031 1.00 49.07 C
ATOM 3292 O ILE G 499 -11.282 1.398 -45.253 1.00 58.45 O
ATOM 3293 N ASN G 500 -12.183 0.764 -43.288 1.00 51.02 N
ATOM 3294 CA ASN G 500 -12.992 -0.307 -43.857 1.00 52.06 C
ATOM 3295 CB ASN G 500 -13.500 -1.238 -42.748 1.00 20.00 C
ATOM 3296 CG ASN G 500 -14.173 -2.487 -43.292 1.00 20.00 C
ATOM 3297 OD1 ASN G 500 -13.795 -3.005 -44.342 1.00 20.00 O
ATOM 3298 ND2 ASN G 500 -15.127 -3.019 -42.536 1.00 20.00 N
ATOM 3299 C ASN G 500 -14.161 0.250 -44.659 1.00 48.31 C
ATOM 3300 O ASN G 500 -14.645 -0.386 -45.596 1.00 56.89 O
ATOM 3301 N GLN G 501 -14.582 1.461 -44.312 1.00 55.87 N
ATOM 3302 CA GLN G 501 -15.607 2.160 -45.074 1.00 53.55 C
ATOM 3303 CB GLN G 501 -16.243 3.258 -44.222 1.00 20.00 C
ATOM 3304 CG GLN G 501 -17.012 2.741 -43.015 1.00 20.00 C
ATOM 3305 CD GLN G 501 -17.674 3.857 -42.226 1.00 20.00 C
ATOM 3306 OE1 GLN G 501 -17.178 4.985 -42.189 1.00 20.00 O
ATOM 3307 NE2 GLN G 501 -18.772 3.536 -41.553 1.00 20.00 N
ATOM 3308 C GLN G 501 -15.030 2.751 -46.357 1.00 45.67 C
ATOM 3309 O GLN G 501 -15.627 2.633 -47.429 1.00 58.31 O
ATOM 3310 N SE G 502 -13.824 3.303 -46.258 1.00 43.44 N
ATOM 3311 CA SER G 502 -13.117 3.801 -47.432 1.00 45.40 C
ATOM 3312 CB SER G 502 -11.789 4.468 -47.045 1.00 20.00 C
ATOM 3313 OG SER G 502 -10.928 3.572 -46.361 1.00 20.00 O
ATOM 3314 C SER G 502 -12.891 2.677 -48.436 1.00 55.15 C
ATOM 3315 O SER G 502 -13.234 2.819 -49.610 1.00 52.57 O
ATOM 3316 N LEU G 503 -12.552 1.495 -47.922 1.00 55.35 N
ATOM 3317 CA LEU G 503 -12.227 0.349 -48.768 1.00 52.12 C
ATOM 3318 CB LEU G 503 -11.591 -0.778 -47.943 1.00 20.00 C
ATOM 3319 CG LEU G 503 -10.187 -0.535 -47.373 1.00 20.00 C
ATOM 3320 CD 1 LEU G 503 -9.810 -1.609 -46.357 1.00 20.00 C
ATOM 3321 CD2 LEU G 503 -9.144 -0.458 -48.481 1.00 20.00 C
ATOM 3322 C LEU G 503 -13.471 -0.159 -49.489 1.00 55.74 C
ATOM 3323 O LEU G 503 -13.402 -0.586 -50.642 1.00 57.75 O
ATOM 3324 N ALA G 504 -14.618 -0.046 -48.826 1.00 57.22 N
ATOM 3325 CA ALA G 504 -15.893 -0.410 -49.436 1.00 59.12 C
ATOM 3326 CB ALA G 504 -16.981 -0.532 -48.377 1.00 20.00 C
ATOM 3327 C ALA G 504 -16.293 0.605 -50.499 1.00 58.10 C
ATOM 3328 O ALA G 504 -16.773 0.241 -51.573 1.00 63.64 O
ATOM 3329 N PHE G 505 -16.075 1.881 -50.198 1.00 58.17 N
ATOM 3330 CA PHE G 505 -16.303 2.940 -51.171 1.00 56.56 C
ATOM 3331 CB PHE G 505 -15.991 4.309 -50.564 1.00 20.00 C
ATOM 3332 CG PHE G 505 -16.870 4.665 -49.405 1.00 20.00 C
ATOM 3333 CD1 PHE G 505 -18.185 5.035 -49.615 1.00 20.00 C
ATOM 3334 CE1 PHE G 505 -19.045 5.205 -48.555 1.00 20.00 C
ATOM 3335 CZ PHE G 505 -18.617 4.934 -47.269 1.00 20.00 C
ATOM 3336 CE2 PHE G 505 -17.314 4.545 -47.047 1.00 20.00 C ATOM 3337 CD2 PHE G 505 -16.446 4.423 -48.109 1.00 20.00 C
ATOM 3338 C PHE G 505 -15.462 2.715 -52.416 1.00 60.12 C
ATOM 3339 O PHE G 505 -15.922 2.939 -53.535 1.00 65.46 O
ATOM 3340 N ILE G 506 -14.235 2.242 -52.213 1.00 56.10 N
ATOM 3341 CA ILE G 506 -13.325 1.960 -53.320 1.00 57.32 C
ATOM 3342 CB ILE G 506 -11.911 1.590 -52.825 1.00 20.00 C
ATOM 3343 CGI ILE G 506 -11.167 2.839 -52.352 1.00 20.00 C
ATOM 3344 CD 1 ILE G 506 -10.010 2.533 -51.425 1.00 20.00 C
ATOM 3345 CG2 ILE G 506 -11.126 0.882 -53.925 1.00 20.00 C
ATOM 3346 C ILE G 506 -13.845 0.812 -54.170 1.00 67.33 C
ATOM 3347 O ILE G 506 -13.674 0.803 -55.390 1.00 76.99 O
ATOM 3348 N A G G 507 -14.325 -0.230 -53.503 1.00 67.87 N
ATOM 3349 CA ARG G 507 -14.920 -1.360 -54.195 1.00 62.11 C
ATOM 3350 CB ARG G 507 -15.328 -2.440 -53.196 1.00 20.00 C
ATOM 3351 CG ARG G 507 -14.151 -3.082 -52.491 1.00 20.00 C
ATOM 3352 CD ARG G 507 -14.592 -4.218 -51.585 1.00 20.00 C
ATOM 3353 NE ARG G 507 -13.453 -4.836 -50.911 1.00 20.00 N
ATOM 3354 CZ ARG G 507 -13.555 -5.749 -49.950 1.00 20.00 C
ATOM 3355 NH1 ARG G 507 -14.748 -6.221 -49.609 1.00 20.00 N
ATOM 3356 NH2 ARG G 507 -12.459 -6.278 -49.422 1.00 20.00 N
ATOM 3357 C ARG G 507 -16.119 -0.920 -55.026 1.00 67.30 C
ATOM 3358 O ARG G 507 -16.131 -1.079 -56.247 1.00 67.02 O
ATOM 3359 N LYS G 508 -17.080 -0.274 -54.375 1.00 66.83 N
ATOM 3360 CA LYS G 508 -18.220 0.295 -55.078 1.00 68.12 C
ATOM 3361 CB LYS G 508 -19.052 1.156 -54.133 1.00 20.00 C
ATOM 3362 CG LYS G 508 -19.813 0.362 -53.096 1.00 20.00 C
ATOM 3363 CD LYS G 508 -20.707 1.269 -52.270 1.00 20.00 C
ATOM 3364 CE LYS G 508 -21.508 0.479 -51.248 1.00 20.00 C
ATOM 3365 NZ LYS G 508 -22.370 1.366 -50.421 1.00 20.00 N
ATOM 3366 C LYS G 508 -17.758 1.131 -56.261 1.00 65.22 C
ATOM 3367 O LYS G 508 -18.149 0.880 -57.402 1.00 72.34 O
ATOM 3368 N SER G 509 -16.859 2.071 -55.990 1.00 64.87 N
ATOM 3369 CA SER G 509 -16.316 2.939 -57.028 1.00 56.47 C
ATOM 3370 CB SER G 509 -15.268 3.896 -56.442 1.00 20.00 C
ATOM 3371 OG SER G 509 -14.170 3.190 -55.888 1.00 20.00 O
ATOM 3372 C SER G 509 -15.736 2.147 -58.205 1.00 56.96 C
ATOM 3373 O SER G 509 -16.064 2.412 -59.363 1.00 65.57 O
ATOM 3374 N ASP G 510 -14.906 1.154 -57.902 1.00 64.34 N
ATOM 3375 CA ASP G 510 -14.282 0.340 -58.939 1.00 64.83 C
ATOM 3376 CB ASP G 510 -13.338 -0.690 -58.316 1.00 20.00 C
ATOM 3377 CG ASP G 510 -12.073 -0.063 -57.768 1.00 20.00 C
ATOM 3378 OD1 ASP G 510 -11.789 1.104 -58.112 1.00 20.00 O
ATOM 3379 OD2 ASP G 510 -11.361 -0.735 -56.993 1.00 20.00 O
ATOM 3380 C ASP G 510 -15.339 -0.362 -59.782 1.00 62.11 C
ATOM 3381 O ASP G 510 -15.346 -0.251 -61.008 1.00 67.61 O
ATOM 3382 N GLU G 511 -16.244 -1.067 -59.112 1.00 64.95 N
ATOM 3383 CA GLU G 511 -17.319 -1.774 -59.791 1.00 60.64 C
ATOM 3384 CB GLU G 511 -18.359 -2.259 -58.780 1.00 20.00 C
ATOM 3385 CG GLU G 511 -17.818 -3.293 -57.801 1.00 20.00 C
ATOM 3386 CD GLU G 511 -18.840 -3.723 -56.760 1.00 20.00 C
ATOM 3387 OE1 GLU G 511 -19.857 -3.017 -56.585 1.00 20.00 O
ATOM 3388 OE2 GLU G 511 -18.603 -4.746 -56.083 1.00 20.00 O
ATOM 3389 C GLU G 511 -17.970 -0.888 -60.842 1.00 59.91 C
ATOM 3390 O GLU G 511 -18.090 -1.278 -62.003 1.00 55.45 O
ATOM 3391 N LEU G 512 -18.270 0.349 -60.460 1.00 44.35 N
ATOM 3392 CA LEU G 512 -18.978 1.259 -61.346 1.00 49.60 C
ATOM 3393 CB LEU G 512 -19.424 2.511 -60.590 1.00 20.00 C
ATOM 3394 CG LEU G 512 -20.377 2.256 -59.416 1.00 20.00 C
ATOM 3395 CD1 LEU G 512 -20.747 3.550 -58.696 1.00 20.00 C
ATOM 3396 CD2 LEU G 512 -21.624 1.499 -59.858 1.00 20.00 C ATOM 3397 C LEU G 512 -18.128 1.626 -62.557 1.00 58.00 C
ATOM 3398 O LEU G 512 -18.542 1.415 -63.696 1.00 55.11 O
ATOM 3399 N LEU G 513 -16.883 2.015 -62.305 1.00 57.91 N
ATOM 3400 CA LEU G 513 -15.963 2.384 -63.378 1.00 57.49 C
ATOM 3401 CB LEU G 513 -14.609 2.810 -62.801 1.00 20.00 C
ATOM 3402 CG LEU G 513 -14.558 4.136 -62.038 1.00 20.00 C
ATOM 3403 CD1 LEU G 513 -13.242 4.263 -61.282 1.00 20.00 C
ATOM 3404 CD2 LEU G 513 -14.743 5.302 -62.996 1.00 20.00 C
ATOM 3405 C LEU G 513 -15.775 1.231 -64.362 1.00 58.78 C
ATOM 3406 O LEU G 513 -15.707 1.437 -65.574 1.00 59.88 O
ATOM 3407 N HIS G 514 -15.708 0.015 -63.829 1.00 60.07 N
ATOM 3408 CA HIS G 514 -15.540 -1.175 -64.652 1.00 62.82 C
ATOM 3409 CB HIS G 514 -15.189 -2.383 -63.782 1.00 20.00 C
ATOM 3410 CG HIS G 514 -13.924 -2.217 -63.001 1.00 20.00 C
ATOM 3411 ND1 HIS G 514 -12.683 -2.154 -63.598 1.00 20.00 N
ATOM 3412 CE1 HIS G 514 -11.757 -2.005 -62.668 1.00 20.00 C
ATOM 3413 NE2 HIS G 514 -12.351 -1.975 -61.489 1.00 20.00 N
ATOM 3414 CD2 HIS G 514 -13.706 -2.113 -61.669 1.00 20.00 C
ATOM 3415 C HIS G 514 -16.796 -1.465 -65.463 1.00 65.10 C
ATOM 3416 O HIS G 514 -16.745 -2.170 -66.470 1.00 66.73 O
ATOM 3417 N ASN G 515 -17.926 -0.941 -65.000 1.00 63.45 N
ATOM 3418 CA ASN G 515 -19.179 -1.062 -65.732 1.00 56.53 C
ATOM 3419 CB ASN G 515 -20.370 -0.925 -64.783 1.00 20.00 C
ATOM 3420 CG ASN G 515 -20.503 -2.107 -63.845 1.00 20.00 C
ATOM 3421 OD1 ASN G 515 -19.979 -3.190 -64.113 1.00 20.00 O
ATOM 3422 ND2 ASN G 515 -21.206 -1.906 -62.734 1.00 20.00 N
ATOM 3423 C ASN G 515 -19.289 -0.043 -66.860 1.00 60.06 C
ATOM 3424 O ASN G 515 -19.825 -0.335 -67.928 1.00 66.48 O
ATOM 3425 N VAL G 516 -18.818 1.168 -66.598 1.00 54.29 N
ATOM 3426 CA VAL G 516 -18.783 2.200 -67.620 1.00 52.70 C
ATOM 3427 CB VAL G 516 -18.233 3.518 -67.056 1.00 20.00 C
ATOM 3428 CGI VAL G 516 -18.151 4.566 -68.153 1.00 20.00 C
ATOM 3429 CG2 VAL G 516 -19.098 4.003 -65.904 1.00 20.00 C
ATOM 3430 C VAL G 516 -17.910 1.753 -68.784 1.00 60.10 C
ATOM 3431 O VAL G 516 -18.340 1.765 -69.937 1.00 61.55 O
ATOM 3432 N ASN G 517 -16.733 1.232 -68.455 1.00 69.10 N
ATOM 3433 CA ASN G 517 -15.793 0.770 -69.466 1.00 67.75 C
ATOM 3434 CB ASN G 517 -14.564 0.137 -68.807 1.00 20.00 C
ATOM 3435 CG ASN G 517 -13.665 1.163 -68.146 1.00 20.00 C
ATOM 3436 OD1 ASN G 517 -13.646 2.330 -68.534 1.00 20.00 O
ATOM 3437 ND2 ASN G 517 -12.873 0.718 -67.177 1.00 20.00 N
ATOM 3438 C ASN G 517 -16.439 -0.209 -70.444 1.00 71.17 C
ATOM 3439 O ASN G 517 -16.188 -0.154 -71.649 1.00 66.42 O
ATOM 3440 N ALA G 518 -17.351 -1.033 -69.935 1.00 72.11 N
ATOM 3441 CA ALA G 518 -18.026 -2.024 -70.764 1.00 74.82 C
ATOM 3442 CB ALA G 518 -18.558 -3.164 -69.912 1.00 20.00 C
ATOM 3443 C ALA G 518 -19.145 -1.399 -71.593 1.00 70.11 C
ATOM 3444 O ALA G 518 -19.363 -1.789 -72.739 1.00 65.18 O
ATOM 3445 N GLY G 519 -19.865 -0.448 -71.006 1.00 56.07 N
ATOM 3446 CA GLY G 519 -20.825 0.357 -71.760 1.00 53.01 C
ATOM 3447 C GLY G 519 -20.156 1.166 -72.856 1.00 63.58 C
ATOM 3448 O GLY G 519 -20.684 1.295 -73.962 1.00 69.35 O
ATOM 3449 N LYS G 520 -18.950 1.647 -72.561 1.00 58.33 N
ATOM 3450 CA LYS G 520 -18.122 2.361 -73.533 1.00 53.44 C
ATOM 3451 CB LYS G 520 -16.848 2.877 -72.865 1.00 20.00 C
ATOM 3452 CG LYS G 520 -17.081 3.958 -71.831 1.00 20.00 C
ATOM 3453 CD LYS G 520 -15.781 4.341 -71.152 1.00 20.00 C
ATOM 3454 CE LYS G 520 -15.984 5.482 -70.173 1.00 20.00 C
ATOM 3455 NZ LYS G 520 -14.753 5.730 -69.376 1.00 20.00 N
ATOM 3456 C LYS G 520 -17.746 1.492 -74.731 1.00 58.24 C ATOM 3457 O LYS G 520 -17.445 2.006 -75.810 1.00 48.60 O
ATOM 3458 N SE G 521 -17.583 0.198 -74.478 1.00 67.19 N
ATOM 3459 CA SER G 521 -17.366 -0.776 -75.542 1.00 60.42 C
ATOM 3460 CB SER G 521 -16.953 -2.131 -74.959 1.00 20.00 C
ATOM 3461 OG SER G 521 -18.028 -2.751 -74.272 1.00 20.00 O
ATOM 3462 C SER G 521 -18.588 -0.942 -76.444 1.00 54.19 C
ATOM 3463 O SER G 521 -18.456 -1.004 -77.664 1.00 65.36 O
ATOM 3464 N THR G 522 -19.761 -1.120 -75.840 1.00 50.09 N
ATOM 3465 CA THR G 522 -21.001 -1.210 -76.608 1.00 57.59 C
ATOM 3466 CB THR G 522 -22.235 -1.431 -75.705 1.00 20.00 C
ATOM 3467 OG1 THR G 522 -22.276 -0.422 -74.689 1.00 20.00 O
ATOM 3468 CG2 THR G 522 -22.196 -2.805 -75.058 1.00 20.00 C
ATOM 3469 C THR G 522 -21.206 0.063 -77.423 1.00 59.16 C
ATOM 3470 O THR G 522 -21.384 0.010 -78.640 1.00 65.90 O
ATOM 3471 N THR G 523 -21.024 1.205 -76.768 1.00 52.59 N
ATOM 3472 CA THR G 523 -21.234 2.498 -77.404 1.00 42.19 C
ATOM 3473 CB THR G 523 -20.961 3.638 -76.423 1.00 20.00 C
ATOM 3474 OG1 THR G 523 -19.578 3.622 -76.049 1.00 20.00 O
ATOM 3475 CG2 THR G 523 -21.819 3.467 -75.180 1.00 20.00 C
ATOM 3476 C THR G 523 -20.352 2.676 -78.636 1.00 48.90 C
ATOM 3477 O THR G 523 -20.786 3.238 -79.641 1.00 63.19 O
ATOM 3478 N ASN G 524 -19.113 2.197 -78.553 1.00 52.51 N
ATOM 3479 CA ASN G 524 -18.206 2.200 -79.701 1.00 57.54 C
ATOM 3480 CB ASN G 524 -16.783 1.822 -79.276 1.00 20.00 C
ATOM 3481 CG ASN G 524 -16.110 2.908 -78.457 1.00 20.00 C
ATOM 3482 OD1 ASN G 524 -16.515 4.069 -78.492 1.00 20.00 O
ATOM 3483 ND2 ASN G 524 -15.087 2.529 -77.699 1.00 20.00 N
ATOM 3484 C ASN G 524 -18.669 1.296 -80.843 1.00 54.12 C
ATOM 3485 O ASN G 524 -18.530 1.652 -82.013 1.00 61.31 O
ATOM 3486 N SER G 525 -19.149 0.102 -80.502 1.00 48.97 N
ATOM 3487 CA SER G 525 -19.658 -0.841 -81.499 1.00 64.81 C
ATOM 3488 CB SER G 525 -20.077 -2.157 -80.838 1.00 61.22 C
ATOM 3489 OG SER G 525 -18.947 -2.929 -80.475 1.00 85.90 O
ATOM 3490 C SER G 525 -20.840 -0.249 -82.254 1.00 69.67 C
ATOM 3491 O SER G 525 -21.093 -0.600 -83.406 1.00 72.60 O
ATOM 3492 N LYS G 526 -21.592 0.610 -81.577 1.00 66.06 N
ATOM 3493 CA LYS G 526 -22.723 1.280 -82.197 1.00 63.67 C
ATOM 3494 CB LYS G 526 -23.675 1.815 -81.127 1.00 70.55 C
ATOM 3495 CG LYS G 526 -24.473 0.741 -80.407 1.00 75.29 C
ATOM 3496 CD LYS G 526 -25.171 1.313 -79.183 1.00 85.03 C
ATOM 3497 CE LYS G 526 -25.776 0.219 -78.325 1.00 82.65 C
ATOM 3498 NZ LYS G 526 -26.303 0.770 -77.048 1.00 73.89 N
ATOM 3499 C LYS G 526 -22.259 2.417 -83.103 1.00 55.36 C
ATOM 3500 O LYS G 526 -22.797 2.611 -84.191 1.00 70.69 O
ATOM 3501 N ILE G 527 -21.275 3.181 -82.638 1.00 57.52 N
ATOM 3502 CA ILE G 527 -20.718 4.273 -83.431 1.00 58.48 C
ATOM 3503 CB ILE G 527 -19.545 4.966 -82.712 1.00 57.00 C
ATOM 3504 CGI ILE G 527 -20.021 5.620 -81.415 1.00 49.07 C
ATOM 3505 CD 1 ILE G 527 -20.228 7.116 -81.534 1.00 46.18 C
ATOM 3506 CG2 ILE G 527 -18.902 6.004 -83.621 1.00 52.63 C
ATOM 3507 C ILE G 527 -20.224 3.758 -84.774 1.00 65.20 C
ATOM 3508 O ILE G 527 -20.455 4.380 -85.810 1.00 66.48 O
ATOM 3509 N TYR G 528 -19.487 2.652 -84.740 1.00 69.78 N
ATOM 3510 CA TYR G 528 -18.985 2.034 -85.961 1.00 72.52 C
ATOM 3511 CB TYR G 528 -18.268 0.712 -85.657 1.00 73.16 C
ATOM 3512 CG TYR G 528 -17.130 0.810 -84.658 1.00 76.94 C
ATOM 3513 CD1 TYR G 528 -16.667 -0.323 -83.994 1.00 70.95 C
ATOM 3514 CE1 TYR G 528 -15.628 -0.245 -83.077 1.00 67.73 C
ATOM 3515 CZ TYR G 528 -15.064 0.981 -82.789 1.00 71.89 C
ATOM 3516 OH TYR G 528 -14.046 1.065 -81.866 1.00 75.44 O ATOM 3517 CE2TY G528 -15.505 2.121 -83.433 1.0077.03 C
ATOM 3518 CD2TYRG528 -16.523 2.029 -84.373 1.0077.84 C
ATOM 3519 C TYRG528 -20.130 1.796 -86.949 1.0071.63 C
ATOM 3520 O TYRG528 -20.150 2.377 -88.036 1.0084.20 O
ATOM 3521 N HIS G 529 -21.116 1.002 -86.534 1.0067.69 N
ATOM 3522 CA HIS G 529 -22.239 0.633 -87.398 1.0060.28 C
ATOM 3523 CB HIS G 529 -23.215 -0.283 -86.659 1.0067.84 C
ATOM 3524 CG HIS G 529 -22.668 -1.645 -86.376 1.0088.54 C
ATOM 3525 ND1HISG529 -23.472 -2.756 -86.236 1.0093.34 N
ATOM 3526 CE1HISG529 -22.725 -3.802 -85.933 1.0086.23 C
ATOM 3527 NE2HISG529 -21.465 -3.410 -85.871 1.0091.95 N
ATOM 3528 CD2HISG529 -21.401 -2.067 -86.151 1.0093.77 C
ATOM 3529 C HIS G 529 -22.987 1.845 -87.944 1.0063.30 C
ATOM 3530 O HIS G 529 -23.453 1.828 -89.083 1.0061.02 O
ATOM 3531 N ILEG530 -23.209 2.842 -87.091 1.0059.79 N
ATOM 3532 CA ILEG530 -23.752 4.121 -87.543 1.0045.70 C
ATOM 3533 CB ILEG530 -23.965 5.095 -86.374 1.0040.57 C
ATOM 3534 CG1ILEG530 -25.130 4.627 -85.499 1.0042.86 C
ATOM 3535 CD1ILEG530 -25.537 5.624 -84.437 1.0051.01 C
ATOM 3536 CG2ILEG530 -24.224 6.501 -86.901 1.0035.31 C
ATOM 3537 C ILEG530 -22.822 4.775 -88.557 1.0057.52 C
ATOM 3538 O ILEG530 -23.260 5.253 -89.604 1.0071.18 O
ATOM 3539 N GLUG531 -21.534 4.787 -88.234 1.0067.55 N
ATOM 3540 CA GLU G 531 -20.508 5.305 -89.129 1.0069.79 C
ATOM 3541 CB GLU G 531 -19.126 5.105 -88.505 1.0084.02 C
ATOM 3542 CG GLU G 531 -18.143 6.228 -88.780 1.00104.22 C
ATOM 3543 CD GLU G 531 -16.823 6.033 -88.058 1.00116.08 C
ATOM 3544 OE1GLUG531 -16.849 5.706 -86.853 1.00118.71 O
ATOM 3545 OE2GLUG531 -15.762 6.211 -88.693 1.00119.69 O
ATOM 3546 C GLU G 531 -20.567 4.624-90.495 1.0064.87 C
ATOM 3547 O GLU G 531 -20.720 5.285 -91.522 1.0055.58 O
ATOM 3548 N ASNG532 -20.409 3.304-90.499 1.0065.70 N
ATOM 3549 CA ASNG532 -20.502 2.516-91.724 1.0064.16 C
ATOM 3550 CB ASNG532 -20.351 1.026 -91.402 1.0060.58 C
ATOM 3551 CG ASNG532 -20.304 0.165 -92.642 1.0067.75 C
ATOM 3552 OD1ASNG532 -19.416 0.312 -93.481 1.0053.59 O
ATOM 3553 ND2ASNG532 -21.285 -0.716 -92.786 1.0061.81 N
ATOM 3554 C ASNG532 -21.809 2.759 -92.472 1.0072.17 C
ATOM 3555 O ASNG532 -21.823 2.885 -93.696 1.0085.75 O
ATOM 3556 N GLU G 533 -22.907 2.812 -91.726 1.0079.68 N
ATOM 3557 CA GLU G 533 -24.220 3.041 -92.307 1.0071.96 C
ATOM 3558 CB GLU G 533 -25.300 2.936 -91.234 1.0067.87 C
ATOM 3559 CG GLU G 533 -26.680 2.653 -91.788 1.0081.94 C
ATOM 3560 CD GLU G 533 -26.710 1.397 -92.632 1.0092.79 C
ATOM 3561 OE1GLUG533 -26.313 0.331 -92.119 1.0095.90 O
ATOM 3562 OE2GLUG533 -26.989 1.501 -93.843 1.0093.14 O
ATOM 3563 C GLU G 533 -24.296 4.406-92.974 1.0068.54 C
ATOM 3564 O GLU G 533 -25.101 4.616 -93.879 1.0079.29 O
ATOM 3565 N ILEG534 -23.542 5.359 -92.440 1.0069.50 N
ATOM 3566 CA ILEG534 -23.498 6.702 -93.003 1.0072.55 C
ATOM 3567 CB ILEG534 -23.070 7.737 -91.956 1.0079.55 C
ATOM 3568 CG1ILEG534 -24.053 7.740-90.784 1.0080.41 C
ATOM 3569 CD1ILEG534 -25.321 6.951 -91.049 1.0089.38 C
ATOM 3570 CG2ILEG534 -22.981 9.118 -92.588 1.0078.63 C
ATOM 3571 C ILEG534 -22.538 6.766 -94.180 1.0074.92 C
ATOM 3572 O ILEG534 -22.589 7.693 -94.987 1.0081.01 O
ATOM 3573 N ALA G 535 -21.648 5.786 -94.255 1.0079.52 N
ATOM 3574 CA ALA G 535 -20.721 5.683 -95.368 1.0082.64 C
ATOM 3575 CB ALA G 535 -19.529 4.824 -94.974 1.0075.39 C
ATOM 3576 C ALA G 535 -21.416 5.115 -96.604 1.0081.39 C ATOM 3577 O ALA G 535 -21.170 5.557 -97.727 1.00 85.54 O
ATOM 3578 N A G G 536 -22.325 4.171 -96.380 1.00 78.41 N
ATOM 3579 CA ARG G 536 -23.115 3.581 -97.457 1.00 83.27 C
ATOM 3580 CB ARG G 536 -23.781 2.287 -96.984 1.00 84.58 C
ATOM 3581 CG ARG G 536 -22.808 1.180 -96.618 1.00103.24 C
ATOM 3582 CD ARG G 536 -23.316 -0.171 -97.085 1.00114.72 C
ATOM 3583 NE ARG G 536 -24.587 -0.515 -96.457 1.00117.80 N
ATOM 3584 CZ ARG G 536 -25.297 -1.600 -96.750 1.00116.66 C
ATOM 3585 NH1 ARG G 536 -24.875 -2.439 -97.685 1.00114.57 N
ATOM 3586 NH2 ARG G 536 -26.417 -1.862 -96.089 1.00116.38 N
ATOM 3587 C ARG G 536 -24.172 4.552 -97.973 1.00 82.20 C
ATOM 3588 O ARG G 536 -24.315 4.737 -99.182 1.00 86.28 O
ATOM 3589 N ILE G 537 -24.941 5.135 -97.058 1.00 77.08 N
ATOM 3590 CA ILE G 537 -25.917 6.156 -97.430 1.00 66.79 C
ATOM 3591 CB ILE G 537 -26.719 6.680 -96.216 1.00 64.76 C
ATOM 3592 CGI ILE G 537 -27.614 5.583 -95.640 1.00 66.92 C
ATOM 3593 CD 1 ILE G 537 -28.487 6.055 -94.493 1.00 70.83 C
ATOM 3594 CG2 ILE G 537 -27.593 7.848 -96.631 1.00 51.02 C
ATOM 3595 C ILE G 537 -25.221 7.330 -98.108 1.00 74.94 C
ATOM 3596 O ILE G 537 -25.824 8.043 -98.907 1.00 97.16 O
ATOM 3597 N LYS G 538 -23.941 7.514 -97.804 1.00 75.09 N
ATOM 3598 CA LYS G 538 -23.162 8.575 -98.427 1.00 90.28 C
ATOM 3599 CB LYS G 538 -22.051 9.054 -97.491 1.00 93.73 C
ATOM 3600 CG LYS G 538 -21.584 10.479 -97.760 1.00 96.60 C
ATOM 3601 CD LYS G 538 -20.446 10.876 -96.830 1.00 95.37 C
ATOM 3602 CE LYS G 538 -20.008 12.313 -97.067 1.00100.63 C
ATOM 3603 NZ LYS G 538 -18.989 12.750 -96.074 1.00 99.58 N
ATOM 3604 C LYS G 538 -22.574 8.114 -99.754 1.00102.20 C
ATOM 3605 O LYS G 538 -21.940 8.891-100.466 1.00112.11 O
ATOM 3606 N LYS G 539 -22.870 6.874-100.126 1.00105.15 N
ATOM 3607 CA LYS G 539 -22.411 6.328-101.396 1.00105.65 C
ATOM 3608 CB LYS G 539 -21.904 4.897-101.211 1.00110.12 C
ATOM 3609 CG LYS G 539 -21.426 4.246-102.498 1.00113.31 C
ATOM 3610 CD LYS G 539 -21.023 2.794-102.284 1.00114.26 C
ATOM 3611 CE LYS G 539 -20.414 2.201-103.550 1.00118.39 C
ATOM 3612 NZ LYS G 539 -19.511 1.047-103.263 1.00121.77 N
ATOM 3613 C LYS G 539 -23.517 6.364-102.444 1.00108.88 C
ATOM 3614 O LYS G 539 -23.375 5.808-103.532 1.00110.77 O
ATOM 3615 N LEU G 540 -24.625 7.011-102.102 1.00111.50 N
ATOM 3616 CA LEU G 540 -25.722 7.201-103.038 1.00110.31 C
ATOM 3617 CB LEU G 540 -27.025 6.656-102.451 1.00101.19 C
ATOM 3618 CG LEU G 540 -26.983 5.200-101.978 1.00 94.26 C
ATOM 3619 CD1 LEU G 540 -28.376 4.691-101.683 1.00 86.40 C
ATOM 3620 CD2 LEU G 540 -26.307 4.311-103.004 1.00 84.54 C
ATOM 3621 C LEU G 540 -25.865 8.679-103.374 1.00118.37 C
ATOM 3622 O LEU G 540 -26.802 9.081-104.064 1.00116.71 O
ATOM 3623 N ILE G 541 -24.894 9.474-102.934 1.00130.80 N
ATOM 3624 CA ILE G 541 -24.844 10.896-103.267 1.00140.48 C
ATOM 3625 CB ILE G 541 -25.701 11.746-102.294 1.00138.99 C
ATOM 3626 CGI ILE G 541 -27.145 11.234-102.257 1.00133.30 C
ATOM 3627 CD 1 ILE G 541 -28.050 11.879-103.291 1.00136.26 C
ATOM 3628 CG2 ILE G 541 -25.680 13.218-102.707 1.00136.12 C
ATOM 3629 C ILE G 541 -23.407 11.410-103.250 1.00144.97 C
ATOM 3630 O ILE G 541 -23.116 12.480-103.783 1.00145.83 O
ATOM 3631 N GLY G 542 -22.519 10.663-102.602 1.00148.77 N
ATOM 3632 CA GLY G 542 -21.119 11.060-102.505 1.00153.58 C
ATOM 3633 C GLY G 542 -20.209 10.194-103.357 1.00160.45 C
ATOM 3634 O GLY G 542 -20.636 9.643-104.372 1.00163.41 O
ATOM 3635 N GLU G 543 -18.962 10.042-102.921 1.00163.83 N
ATOM 3636 CA GLU G 543 -17.983 9.236-103.649 1.00165.52 C ATOM 3637 CB GLU G 543 -16.557 9.674-103.305 1.00158.94 C
ATOM 3642 C GLU G 543 -18.156 7.742-103.381 1.00168.27 C
ATOM 3643 O GLU G 543 -19.116 7.322-102.736 1.00167.37 O
ATOM 3644 N GLN H 26 -24.590 4.282 7.491 1.00 23.62 B N
ATOM 3645 CA GLN H 26 -23.869 3.499 6.449 1.00 23.82 B C
ATOM 3646 CB GLN H 26 -22.633 2.827 7.055 1.00 23.94 B C
ATOM 3647 CG GLN H 26 -21.724 3.775 7.833 1.00 28.83 B C
ATOM 3648 CD GLN H 26 -22.314 4.205 9.165 1.00 36.36 B C
ATOM 3649 OE1 GLN H 26 -23.057 5.183 9.238 1.00 39.09 B O
ATOM 3650 NE2 GLN H 26 -21.891 3.545 10.238 1.00 37.86 B N
ATOM 3651 C GLN H 26 -24.797 2.460 5.813 1.00 23.09 B C
ATOM 3652 O GLN H 26 -25.818 2.096 6.397 1.00 24.21 B O
ATOM 3653 N ASN H 27 -24.543 2.146 4.544 1.00 20.98 B N
ATOM 3654 CA ASN H 27 -25.343 1.173 3.786 1.00 19.70 B C
ATOM 3655 CB ASN H 27 -26.642 1.832 3.269 1.00 20.41 B C
ATOM 3656 CG ASN H 27 -27.524 0.887 2.423 1.00 23.56 B C
ATOM 3657 OD1 ASN H 27 -27.835 -0.233 2.837 1.00 24.42 B O
ATOM 3658 ND2 ASN H 27 -27.836 1.322 1.182 1.00 27.70 B N
ATOM 3659 C ASN H 27 -24.507 0.652 2.619 1.00 18.42 B C
ATOM 3660 O ASN H 27 -24.904 0.783 1.462 1.00 18.47 B O
ATOM 3661 N ILE H 28 -23.291 0.196 2.907 1.00 16.54 B N
ATOM 3662 CA ILE H 28 -22.439 -0.335 1.849 1.00 14.59 B C
ATOM 3663 CB ILE H 28 -20.939 -0.378 2.223 1.00 14.01 B C
ATOM 3664 CGI ILE H 28 -20.746 -0.823 3.674 1.00 15.60 B C
ATOM 3665 CD1 ILE H 28 -20.221 -2.240 3.815 1.00 16.26 B C
ATOM 3666 CG2 ILE H 28 -20.276 0.964 1.942 1.00 12.57 B C
ATOM 3667 C ILE H 28 -22.898 -1.700 1.360 1.00 13.86 B C
ATOM 3668 O ILE H 28 -23.458 -2.494 2.119 1.00 13.70 B O
ATOM 3669 N TH H 29 -22.868 -1.850 0.044 1.00 13.23 B N
ATOM 3670 CA TH H 29 -23.353 -3.045 -0.612 1.00 12.65 B C
ATOM 3671 CB TH H 29 -24.751 -2.816 -1.206 1.00 12.69 B C
ATOM 3672 OG1 THR H 29 -25.331 -1.643 -0.623 1.00 12.62 B O
ATOM 3673 CG2 THR H 29 -25.650 -4.012 -0.934 1.00 12.92 B C
ATOM 3674 C THR H 29 -22.392 -3.355 -1.741 1.00 12.47 B C
ATOM 3675 O THR H 29 -21.760 -2.457 -2.297 1.00 12.53 B O
ATOM 3676 N GLU H 30 -22.300 -4.626 -2.095 1.00 11.98 B N
ATOM 3677 CA GLU H 30 -21.668 -5.007 -3.338 1.00 11.68 B C
ATOM 3678 CB GLU H 30 -20.393 -5.803 -3.049 1.00 11.98 B C
ATOM 3679 CG GLU H 30 -19.274 -5.593 -4.058 1.00 13.38 B C
ATOM 3680 CD GLU H 30 -17.927 -6.054 -3.533 1.00 16.03 B C
ATOM 3681 OE1 GLU H 30 -17.846 -7.190 -3.019 1.00 16.65 B O
ATOM 3682 OE2 GLU H 30 -16.968 -5.253 -3.563 1.00 17.06 B O
ATOM 3683 C GLU H 30 -22.655 -5.860 -4.114 1.00 11.39 B C
ATOM 3684 O GLU H 30 -23.316 -6.727 -3.542 1.00 11.50 B O
ATOM 3685 N GLU H 31 -22.850 -5.534 -5.384 1.00 11.11 B N
ATOM 3686 CA GLU H 31 -23.602 -6.419 -6.248 1.00 11.06 B C
ATOM 3687 CB GLU H 31 -24.955 -5.813 -6.611 1.00 11.48 B C
ATOM 3688 CG GLU H 31 -25.093 -5.417 -8.063 1.00 13.90 B C
ATOM 3689 CD GLU H 31 -26.500 -4.981 -8.404 1.00 17.27 B C
ATOM 3690 OE1 GLU H 31 -27.092 -5.567 -9.335 1.00 17.55 B O
ATOM 3691 OE2 GLU H 31 -27.053 -4.130 -7.676 1.00 18.73 B O
ATOM 3692 C GLU H 31 -22.828 -6.839 -7.485 1.00 10.47 B C
ATOM 3693 O GLU H 31 -22.042 -6.071 -8.040 1.00 10.12 B O
ATOM 3694 N PHE H 32 -22.962 -8.116 -7.818 1.00 10.15 B N
ATOM 3695 CA PHE H 32 -22.042 -8.788 -8.716 1.00 9.62 B C
ATOM 3696 CB PHE H 32 -21.692 -10.167 -8.158 1.00 9.42 B C
ATOM 3697 CG PHE H 32 -21.130 -11.106 -9.179 1.00 9.27 B C
ATOM 3698 CD1 PHE H 32 -19.865 -10.896 -9.702 1.00 9.37 B C
ATOM 3699 CE1 PHE H 32 -19.315 -11.784 -10.605 1.00 9.52 B C
ATOM 3700 CZ PHE H 32 -20.027 -12.905 -10.989 1.00 9.82 B C ATOM 3701 CE2 PHE H 32 -21.294 -13.127 -10.472 1.00 10.13 B C
ATOM 3702 CD2 PHE H 32 -21.822 -12.250 -9.544 1.00 10.06 B C
ATOM 3703 C PHE H 32 -22.707 -8.941 -10.074 1.00 9.64 B C
ATOM 3704 O PHE H 32 -23.887 -9.282 -10.159 1.00 9.84 B O
ATOM 3705 N TY H 33 -21.965 -8.638 -11.132 1.00 9.59 B N
ATOM 3706 CA TYR H 33 -22.526 -8.672 -12.474 1.00 9.67 B C
ATOM 3707 CB TYR H 33 -22.259 -7.360 -13.207 1.00 9.52 B C
ATOM 3708 CG TYR H 33 -23.038 -6.196 -12.645 1.00 10.94 B C
ATOM 3709 CD1 TYR H 33 -22.482 -5.372 -11.677 1.00 12.23 B C
ATOM 3710 CE1 TYR H 33 -23.198 -4.323 -11.137 1.00 12.93 B C
ATOM 3711 CZ TYR H 33 -24.510 -4.129 -11.510 1.00 13.47 B C
ATOM 3712 OH TYR H 33 -25.231 -3.093 -10.963 1.00 14.54 B O
ATOM 3713 CE2 TYR H 33 -25.100 -4.963 -12.436 1.00 13.56 B C
ATOM 3714 CD2 TYR H 33 -24.373 -6.006 -12.976 1.00 12.96 B C
ATOM 3715 C TYR H 33 -22.001 -9.853 -13.273 1.00 9.94 B C
ATOM 3716 O TYR H 33 -20.998 -9.747 -13.978 1.00 10.16 B O
ATOM 3717 N GLN H 34 -22.714 -10.969 -13.184 1.00 10.06 B N
ATOM 3718 CA GLN H 34 -22.191 -12.249 -13.632 1.00 10.01 B C
ATOM 3719 CB GLN H 34 -23.190 -13.361 -13.327 1.00 10.22 B C
ATOM 3720 CG GLN H 34 -22.760 -14.720 -13.829 1.00 11.12 B C
ATOM 3721 CD GLN H 34 -23.604 -15.836 -13.257 1.00 13.13 B C
ATOM 3722 OE1 GLN H 34 -24.746 -16.042 -13.673 1.00 14.24 B O
ATOM 3723 NE2 GLN H 34 -23.057 -16.550 -12.278 1.00 13.79 B N
ATOM 3724 C GLN H 34 -21.889 -12.220 -15.123 1.00 9.94 B C
ATOM 3725 O GLN H 34 -21.096 -13.018 -15.622 1.00 10.08 B O
ATOM 3726 N SER H 35 -22.564 -11.324 -15.836 1.00 9.87 B N
ATOM 3727 CA SER H 35 -22.458 -11.253 -17.290 1.00 9.91 B C
ATOM 3728 CB SER H 35 -23.743 -10.676 -17.889 1.00 10.03 B C
ATOM 3729 OG SER H 35 -24.034 -9.401 -17.343 1.00 10.81 B O
ATOM 3730 C SER H 35 -21.256 -10.410 -17.713 1.00 9.56 B C
ATOM 3731 O SER H 35 -21.002 -10.214 -18.903 1.00 9.59 B O
ATOM 3732 N THR H 36 -20.539 -9.892 -16.724 1.00 9.21 B N
ATOM 3733 CA THR H 36 -19.420 -8.996 -16.964 1.00 9.06 B C
ATOM 3734 CB THR H 36 -19.817 -7.536 -16.686 1.00 9.49 B C
ATOM 3735 OG1 THR H 36 -20.874 -7.149 -17.573 1.00 10.82 B O
ATOM 3736 CG2 THR H 36 -18.629 -6.609 -16.883 1.00 9.45 B C
ATOM 3737 C THR H 36 -18.292 -9.403 -16.029 1.00 8.77 B C
ATOM 3738 O THR H 36 -17.298 -8.693 -15.882 1.00 8.60 B o
ATOM 3739 N CYS H 37 -18.457 - 10.572 -15.415 1.00 8.69 B N
ATOM 3740 CA CYS H 37 -17.594 -11.011 -14.327 1.00 8.69 B C
ATOM 3741 CB CYS H 37 -16.509 -11.955 -14.846 1.00 8.81 B c
ATOM 3742 SG CYS H 37 -15.737 -12.977 -13.569 1.00 10.80 B s
ATOM 3743 C CYS H 37 -16.958 ■ -9.820 -13.631 1.00 8.27 B c
ATOM 3744 O CYS H 37 -15.735 -9.671 -13.628 1.00 8.27 B o
ATOM 3745 N SER H 38 -17.796 - ■8.950 -13.080 1.00 7.92 B N
ATOM 3746 CA SER H 38 -17.309 -7.784 -12.360 1.00 7.51 B c
ATOM 3747 CB SER H 38 -17.130 -6.595 -13.308 1.00 7.63 B c
ATOM 3748 OG SER H 38 -18.369 -6.193 -13.864 1.00 8.54 B o
ATOM 3749 C SER H 38 -18.227 - 7.411 -11.207 1.00 7.02 B c
ATOM 3750 O SER H 38 -19.404 - ■7.771 -11.192 1.00 6.83 B o
ATOM 3751 N ALA H 39 -17.647 -6.784 -10.191 1.00 6.64 B N
ATOM 3752 CA ALA H 39 -18.371 -6.478 -8.969 1.00 6.58 B c
ATOM 3753 CB ALA H 39 -17.843 -7.320 -7.817 1.00 6.67 B c
ATOM 3754 C ALA H 39 -18.242 -4.995 -8.651 1.00 6.93 B c
ATOM 3755 O ALA H 39 -17.217 -4.378 -8.944 1.00 7.38 B o
ATOM 3756 N VAL H 40 -19.333 -4.401 -8.179 1.00 6.87 B N
ATOM 3757 CA VAL H 40 -19.316 -3.008 -7.746 1.00 6.55 B c
ATOM 3758 CB VAL H 40 -20.208 -2.122 -8.635 1.00 6.22 B c
ATOM 3759 CGI VAL H 40 -20.465 -0.783 -7.959 1.00 6.52 B C ATOM 3760 CG2 VAL H 40 -19.564 -1.921 -9.998 1.00 6.62 B C ATOM 3761 C VAL H 40 -19.743 -2.862 -6.290 1.00 6.73 B C
ATOM 3762 O VAL H 40 -20.805 -3.340 -5.891 1.00 6.83 B o
ATOM 3763 N SER H 41 -18.883 -2.240 - 5.492 1.00 6.86 B N
ATOM 3764 CA SE H 41 -19.251 -1.825 -4.148 1.00 6.75 B C
ATOM 3765 CB SER H 41 -18.020 -1.779 -3.242 1.00 7.06 B c
ATOM 3766 OG SER H 41 -16.905 -2.388 -3.866 1.00 7.50 B o
ATOM 3767 C SER H 41 -19.922 -0.461 - 4.180 1.00 6.56 B c
ATOM 3768 O SER H 41 -19.392 0.490 - 4.756 1.00 6.08 B o
ATOM 3769 N LYS H 42 -21.097 -0.378 - 3.565 1.00 7.02 B N
ATOM 3770 CA LYS H 42 -21.938 0.810 -3.662 1.00 7.83 B c
ATOM 3771 CB LYS H 42 -23.296 0.459 -4.269 1.00 8.15 B c
ATOM 3772 CG LYS H 42 -23.226 -0.171 -5.641 1.00 9.75 B c
ATOM 3773 CD LYS H 42 -24.621 -0.473 -6.153 1.00 12.62 B c
ATOM 3774 CE LYS H 42 -24.579 -1.069 -7.548 1.00 14.04 B c
ATOM 3775 NZ LYS H 42 -25.858 -0.856 -8.279 1.00 14.96 B N
ATOM 3776 C LYS H 42 -22.143 1.444 - 2.290 1.00 7.80 B c
ATOM 3777 O LYS H 42 -21.947 0.798 - 1.258 1.00 8.15 B o
ATOM 3778 N GLY H 43 -22.594 2.696■ -2.290 1.00 7.59 B N
ATOM 3779 CA GLY H 43 -23.140 3.321 -1.090 1.00 7.35 B c
ATOM 3780 C GLY H 43 -22.131 4.200 - ■0.378 1.00 7.10 B c
ATOM 3781 O GLY H 43 -22.239 4.439 0.824 1.00 7.13 B o
ATOM 3782 N TYR H 44 -21.173 4.723 - ■1.136 1.00 7.01 B N
ATOM 3783 CA TYR H 44 -20.106 5.549 -0.577 1.00 6.89 B c
ATOM 3784 CB TYR H 44 -18.755 5.125 -1.160 1.00 6.88 B c
ATOM 3785 CG TYR H 44 -18.296 3.748 -0.732 1.00 6.41 B c
ATOM 3786 CDl TYR H 44 -18.340 2.676 -1.615 1.00 6.62 B c
ATOM 3787 CE1 TYR H 44 -17.871 1.427 -1.245 1.00 6.48 B c
ATOM 3788 CZ TYR H 44 -17.312 1.253 0.005 1.00 6.88 B c
ATOM 3789 OH TYR H 44 -16.834 0.020 0.386 1.00 7.50 B o
ATOM 3790 CE2 TYR H 44 -17.197 2.318 0.870 1.00 6.68 B c
ATOM 3791 CD2 TYR H 44 -17.670 3.559 0.492 1.00 5.91 B c
ATOM 3792 C TYR H 44 -20.357 7.026 - 0.886 1.00 6.86 B c
ATOM 3793 O TYR H 44 -20.912 7.354 - ■1.933 1.00 7.14 B o
ATOM 3794 N LEU H 45 -19.834 7.916 - 0.045 1.00 6.44 B N
ATOM 3795 CA LEU H 45 -20.073 9.356 -0.205 1.00 6.12 B c
ATOM 3796 CB LEU H 45 -20.896 9.917 0.966 1.00 6.31 B c
ATOM 3797 CG LEU H 45 -22.355 9.463 1.108 1.00 6.38 B c
ATOM 3798 CDl LEU H 45 -22.859 9.699 2.524 1.00 7.05 B c
ATOM 3799 CD2 LEU H 45 -23.256 10.158 0.096 1.00 7.05 B c
ATOM 3800 C LEU H 45 -18.791 10.173 -0.413 1.00 5.84 B c
ATOM 3801 O LEU H 45 -17.966 10.289 0.493 1.00 5.94 B o
ATOM 3802 N SER H 46 -18.764 10.924 -1.512 1.00 5.43 B N
ATOM 3803 CA SER H 46 -17.528 11.442 -2.112 1.00 5.26 B c
ATOM 3804 CB SER H 46 -17.801 11.821 -3.568 1.00 5.21 B c
ATOM 3805 OG SER H 46 -18.827 12.800 -3.647 1.00 4.95 B o
ATOM 3806 C SER H 46 -17.113 12.696 ■ -1.355 1.00 5.51 B c
ATOM 3807 O SER H 46 -17.968 13.359 -0.771 1.00 6.03 B o
ATOM 3808 N ALA H 47 -15.850 13.103 -1.424 1.00 5.24 B N
ATOM 3809 CA ALA H 47 -15.530 14.323 -0.704 1.00 4.83 B c
ATOM 3810 CB ALA H 47 -16.269 14.344 0.622 1.00 5.01 B c
ATOM 3811 C ALA H 47 -14.089 14.763 -0.512 1.00 4.35 B c
ATOM 3812 O ALA H 47 -13.178 13.936 -0.449 1.00 4.45 B o
ATOM 3813 N LEU H 48 -13.989 15.994 -0.016 1.00 3.67 B N
ATOM 3814 CA LEU H 48 -12.719 16.625 0.308 1.00 3.15 B c
ATOM 3815 CB LEU H 48 -12.390 17.712 -0.720 1.00 2.78 B c
ATOM 3816 CG LEU H 48 -12.856 17.464 -2.159 1.00 2.18 B c
ATOM 3817 CDl LEU H 48 -12.396 18.583 -3.082 1.00 2.00 B c
ATOM 3818 CD2 LEU H 48 -12.378 16.109 -2.666 1.00 3.94 B c
ATOM 3819 C LEU H 48 -12.768 17.232 1.707 1.00 3.06 B c
ATOM 3820 O LEU H 48 -13.519 18.174 1.961 1.00 3.27 B o ATOM 3821 N A G H 49 -11.879 16.758 2.571 1.00 2.91 B N
ATOM 3822 CA ARG H 49 -11.733 17.305 3.912 1.00 2.88 B C
ATOM 3823 CB ARG H 49 -10.649 16.538 4.668 1.00 2.69 B C
ATOM 3824 CG ARG H 49 -11.032 16.140 6.075 1.00 2.15 B c
ATOM 3825 CD ARG H 49 -9.882 16.395 7.026 1.00 2.00 B c
ATOM 3826 NE ARG H 49 -9.728 17.816 7.320 1.00 5.18 B N
ATOM 3827 CZ ARG H 49 -8.580 18.478 7.231 1.00 7.68 B c
ATOM 3828 NH1 ARG H 49 -7.481 17.849 6.838 1.00 8.32 B N
ATOM 3829 NH2 ARG H 49 -8.521 19.756 7.575 1.00 8.12 B N
ATOM 3830 C ARG H 49 -11.364 18.780 3.843 1.00 3.09 B C
ATOM 3831 O ARG H 49 -10.497 19.175 3.064 1.00 3.08 B o
ATOM 3832 N THR H 50 -12.022 19.593 4.661 1.00 3.37 B N
ATOM 3833 CA THR H 50 -11.594 20.970 4.855 1.00 3.55 B C
ATOM 3834 CB THR H 50 -12.413 21.946 3.998 1.00 3.25 B c
ATOM 3835 OG1 THR H 50 -13.807 21.633 4.109 1.00 2.66 B o
ATOM 3836 CG2 THR H 50 -11.992 21.844 2.543 1.00 3.46 B c
ATOM 3837 C THR H 50 -11.665 21.395 6.313 1.00 4.07 B c
ATOM 3838 O THR H 50 -11.171 22.462 6.678 1.00 4.35 B o
ATOM 3840 CA GLY H 51 -13.255 22.675 6.821 1.00 4.78 B c
ATOM 3841 C GLY H 51 -11.930 22.228 7.407 1.00 4.98 B c
ATOM 3842 O GLY H 51 -11.589 21.046 7.365 1.00 5.00 B o
ATOM 3843 N TRP H 52 -11.162 23.180 7.925 1.00 5.34 B N
ATOM 3844 CA TRP H 52 -9.845 22.878 8.465 1.00 5.42 B c
ATOM 3845 CB TRP H 52 -8.754 23.540 7.632 1.00 5.75 B c
ATOM 3846 CG TRP H 52 -8.691 23.029 6.243 1.00 6.38 B c
ATOM 3847 CD1 TRP H 52 -9.100 23.678 5.117 1.00 7.27 B c
ATOM 3848 NE1 TRP H 52 -8.926 22.875 4.019 1.00 7.46 B N
ATOM 3849 CE2 TRP H 52 -8.445 21.660 4.430 1.00 7.15 B c
ATOM 3850 CD2 TRP H 52 -8.315 21.710 5.832 1.00 7.02 B c
ATOM 3851 CE3 TRP H 52 -7.799 20.595 6.500 1.00 6.83 B c
ATOM 3852 CZ3 TRP H 52 -7.466 19.473 5.761 1.00 6.73 B c
ATOM 3853 CH2 TRP H 52 -7.634 19.445 4.372 1.00 7.13 B c
ATOM 3854 CZ2 TRP H 52 -8.111 20.529 3.689 1.00 6.82 B c
ATOM 3855 C TRP H 52 -9.723 23.329 9.905 1.00 5.34 B C
ATOM 3856 O TRP H 52 -10.279 24.359 10.289 1.00 5.47 B o
ATOM 3857 N TYR H 53 -8.800 22.695 10.615 1.00 5.29 B N
ATOM 3858 CA TYR H 53 -8.531 23.038 11.997 1.00 5.58 B c
ATOM 3859 CB TYR H 53 -9.040 21.934 12.919 1.00 5.51 B c
ATOM 3860 CG TYR H 53 -8.759 22.187 14.377 1.00 6.59 B c
ATOM 3861 CD1 TYR H 53 -9.668 22.879 15.169 1.00 8.25 B c
ATOM 3862 CE1 TYR H 53 -9.440 23.068 16.521 1.00 9.40 B c
ATOM 3863 CZ TYR H 53 -8.293 22.555 17.096 1.00 9.24 B c
ATOM 3864 OH TYR H 53 -8.053 22.750 18.439 1.00 9.61 B o
ATOM 3865 CE2 TYR H 53 -7.360 21.893 16.321 1.00 8.78 B c
ATOM 3866 CD2 TYR H 53 -7.600 21.709 14.971 1.00 7.93 B c
ATOM 3867 C TYR H 53 -7.042 23.256 12.214 1.00 5.74 B c
ATOM 3868 O TYR H 53 -6.259 22.306 12.223 1.00 6.19 B o
ATOM 3869 N THR H 54 -6.645 24.521 12.296 1.00 6.04 B N
ATOM 3870 CA THR H 54 -5.249 24.869 12.519 1.00 6.67 B c
ATOM 3871 CB THR H 54 -5.032 26.391 12.438 1.00 6.97 B c
ATOM 3872 OG1 THR H 54 -4.958 26.793 11.064 1.00 7.51 B o
ATOM 3873 CG2 THR H 54 -3.747 26.788 13.147 1.00 7.98 B c
ATOM 3874 C THR H 54 -4.775 24.360 13.877 1.00 6.97 B c
ATOM 3875 O THR H 54 -5.576 24.173 14.792 1.00 7.32 B o
ATOM 3876 N SER H 55 -3.479 24.086 13.987 1.00 7.24 B N
ATOM 3877 CA SER H 55 -2.811 24.106 15.282 1.00 7.65 B c
ATOM 3878 CB SER H 55 -3.110 22.830 16.072 1.00 7.69 B c
ATOM 3879 OG SER H 55 -2.308 22.754 17.238 1.00 7.51 B o
ATOM 3880 C SER H 55 -1.308 24.309 15.154 1.00 8.03 B c
ATOM 3881 O SER H 55 -0.654 23.695 14.311 1.00 8.43 B o ATOM 3882 N VAL H 56 -0.760 25.106 16.063 1.00 8.14 B N
ATOM 3883 CA VAL H 56 0.600 25.601 15.930 1.00 8.41 B C
ATOM 3884 CB VAL H 56 0.672 27.116 16.193 1.00 8.72 B C
ATOM 3885 CGI VAL H 56 1.868 27.723 15.477 1.00 9.29 B C
ATOM 3886 CG2 VAL H 56 -0.619 27.792 15.756 1.00 9.51 B C
ATOM 3887 C VAL H 56 1.509 24.884 16.917 1.00 8.19 B C
ATOM 3888 O VAL H 56 1.348 25.011 18.129 1.00 8.54 B O
ATOM 3889 N ILE H 57 2.428 24.086 16.389 1.00 7.91 B N
ATOM 3890 CA ILE H 57 3.224 23.192 17.214 1.00 7.64 B C
ATOM 3891 CB ILE H 57 3.175 21.749 16.674 1.00 7.35 B C
ATOM 3892 CGI ILE H 57 1.726 21.302 16.462 1.00 7.25 B C
ATOM 3893 CD1 ILE H 57 1.593 19.930 15.834 1.00 8.42 B C
ATOM 3894 CG2 ILE H 57 3.915 20.799 17.603 1.00 7.52 B C
ATOM 3895 C ILE H 57 4.670 23.670 17.258 1.00 7.69 B C
ATOM 3896 O ILE H 57 5.272 23.936 16.219 1.00 7.79 B O
ATOM 3897 N TH H 58 5.175 23.897 18.467 1.00 7.85 B N
ATOM 3898 CA THR H 58 6.465 24.554 18.659 1.00 8.15 B C
ATOM 3899 CB THR H 58 6.297 25.903 19.383 1.00 8.14 B C
ATOM 3900 OG1 THR H 58 4.946 26.360 19.239 1.00 8.62 B O
ATOM 3901 CG2 THR H 58 7.246 26.943 18.806 1.00 7.94 B C
ATOM 3902 C THR H 58 7.393 23.666 19.485 1.00 8.20 B C
ATOM 3903 O THR H 58 7.051 23.281 20.600 1.00 8.18 B O
ATOM 3904 N ILE H 59 8.565 23.351 18.941 1.00 8.54 B N
ATOM 3905 CA ILE H 59 9.482 22.397 19.572 1.00 9.23 B C
ATOM 3906 CB ILE H 59 9.604 21.112 18.729 1.00 8.92 B C
ATOM 3907 CGI ILE H 59 8.231 20.482 18.496 1.00 9.27 B C
ATOM 3908 CD1 ILE H 59 8.253 19.315 17.533 1.00 10.89 B C
ATOM 3909 CG2 ILE H 59 10.559 20.130 19.387 1.00 8.74 B C
ATOM 3910 C ILE H 59 10.880 23.004 19.691 1.00 10.02 B C
ATOM 3911 O ILE H 59 11.474 23.380 18.684 1.00 10.20 B O
ATOM 3912 N GLU H 60 11.434 23.059 20.898 1.00 10.95 B N
ATOM 3913 CA GLU H 60 12.592 23.923 21.138 1.00 12.13 B C
ATOM 3914 CB GLU H 60 12.914 23.976 22.634 1.00 12.44 B C
ATOM 3915 CG GLU H 60 11.854 24.705 23.444 1.00 15.04 B C
ATOM 3916 CD GLU H 60 12.365 25.173 24.793 1.00 19.34 B C
ATOM 3917 OE1 GLU H 60 12.659 24.309 25.647 1.00 20.63 B O
ATOM 3918 OE2 GLU H 60 12.495 26.401 24.990 1.00 21.19 B O
ATOM 3919 C GLU H 60 13.816 23.509 20.301 1.00 12.46 B C
ATOM 3920 O GLU H 60 14.196 22.336 20.316 1.00 12.68 B O
ATOM 3921 N LEU H 61 14.390 24.428 19.510 1.00 12.80 B N
ATOM 3922 CA LEU H 61 15.786 24.207 19.132 1.00 12.71 B C
ATOM 3923 CB LEU H 61 16.470 25.295 18.316 1.00 12.55 B C
ATOM 3924 CG LEU H 61 17.932 24.803 18.355 1.00 12.39 B C
ATOM 3925 CD1 LEU H 61 18.053 23.370 17.848 1.00 13.14 B C
ATOM 3926 CD2 LEU H 61 18.944 25.717 17.683 1.00 12.50 B C
ATOM 3927 C LEU H 61 16.459 24.114 20.455 1.00 12.94 B C
ATOM 3928 O LEU H 61 16.827 25.135 21.048 1.00 12.78 B O
ATOM 3929 N SER H 62 16.080 23.014 21.081 1.00 13.61 B N
ATOM 3930 CA SER H 62 16.441 22.760 22.447 1.00 14.70 B C
ATOM 3931 CB SER H 62 15.805 21.454 22.924 1.00 14.52 B C
ATOM 3932 OG SER H 62 14.398 21.584 23.034 1.00 14.80 B O
ATOM 3933 C SER H 62 17.947 22.650 22.469 1.00 15.48 B C
ATOM 3934 O SER H 62 18.498 21.677 21.961 1.00 15.50 B O
ATOM 3935 N ASN H 63 18.597 23.777 22.721 1.00 16.61 B N
ATOM 3936 CA ASN H 63 20.030 23.839 22.523 1.00 17.77 B C
ATOM 3937 CB ASN H 63 20.519 25.279 22.439 1.00 17.73 B C
ATOM 3938 CG ASN H 63 21.686 25.433 21.493 1.00 18.52 B C
ATOM 3939 OD1 ASN H 63 22.559 24.567 21.428 1.00 18.29 B O
ATOM 3940 ND2 ASN H 63 21.641 26.467 20.665 1.00 19.40 B N
ATOM 3941 C ASN H 63 20.795 23.070 23.587 1.00 18.53 B C ATOM 3942 O ASN H 63 20.356 22.967 24.732 1.00 18.82 B O
ATOM 3943 N ILE H 64 21.887 22.440 23.169 1.00 19.60 B N
ATOM 3944 CA ILE H 64 22.830 21.832 24.096 1.00 21.04 B C
ATOM 3945 CB ILE H 64 23.599 20.680 23.429 1.00 20.60 B C
ATOM 3946 CGI ILE H 64 22.650 19.824 22.590 1.00 20.13 B C
ATOM 3947 CD1 ILE H 64 23.355 18.820 21.712 1.00 20.19 B C
ATOM 3948 CG2 ILE H 64 24.321 19.843 24.474 1.00 20.74 B C
ATOM 3949 C ILE H 64 23.837 22.859 24.601 1.00 22.58 B C
ATOM 3950 O ILE H 64 24.450 23.577 23.811 1.00 23.07 B O
ATOM 3951 N LYS H 65 24.104 22.827 25.903 1.00 24.21 B N
ATOM 3952 CA LYS H 65 25.356 23.354 26.435 1.00 25.86 B C
ATOM 3953 CB LYS H 65 25.109 24.202 27.686 1.00 25.90 B C
ATOM 3954 CG LYS H 65 23.736 24.015 28.312 1.00 26.69 B c
ATOM 3955 CD LYS H 65 23.556 22.597 28.830 1.00 28.26 B c
ATOM 3956 CE LYS H 65 23.104 22.591 30.281 1.00 28.67 B c
ATOM 3957 NZ LYS H 65 23.397 21.291 30.946 1.00 28.95 B N
ATOM 3958 C LYS H 65 26.377 22.252 26.719 1.00 26.81 B c
ATOM 3959 O LYS H 65 26.297 21.561 27.736 1.00 26.72 B o
ATOM 3960 N GLU H 66 27.382 22.159 25.852 1.00 27.90 B N
ATOM 3961 CA GLU H 66 28.276 21.001 25.793 1.00 28.82 B c
ATOM 3962 CB GLU H 66 29.031 20.991 24.457 1.00 28.88 B c
ATOM 3963 CG GLU H 66 30.531 20.737 24.572 1.00 30.33 B c
ATOM 3964 CD GLU H 66 31.320 21.283 23.391 1.00 33.17 B c
ATOM 3965 OE1 GLU H 66 32.446 20.796 23.151 1.00 35.05 B o
ATOM 3966 OE2 GLU H 66 30.864 22.268 22.775 1.00 33.14 B o
ATOM 3967 C GLU H 66 29.267 21.029 26.954 1.00 29.12 B c
ATOM 3968 O GLU H 66 29.751 22.097 27.329 1.00 29.28 B o
ATOM 3969 N ASN H 67 29.545 19.871 27.547 1.00 29.32 B N
ATOM 3970 CA ASN H 67 30.326 19.847 28.783 1.00 29.39 B c
ATOM 3971 CB ASN H 67 29.525 19.250 29.941 1.00 29.62 B c
ATOM 3972 CG ASN H 67 28.892 20.317 30.814 1.00 29.84 B c
ATOM 3973 OD1 ASN H 67 29.589 21.032 31.534 1.00 29.93 B o
ATOM 3974 ND2 ASN H 67 27.597 20.540 30.625 1.00 29.22 B N
ATOM 3975 C ASN H 67 31.745 19.271 28.698 1.00 29.15 B c
ATOM 3976 O ASN H 67 31.977 18.111 29.044 1.00 29.06 B o
ATOM 3977 N LYS H 68 32.625 20.020 28.036 1.00 28.87 B N
ATOM 3978 CA LYS H 68 34.033 20.170 28.428 1.00 28.78 B c
ATOM 3979 CB LYS H 68 34.334 21.625 28.806 1.00 28.89 B c
ATOM 3980 CG LYS H 68 33.742 22.653 27.846 1.00 29.26 B c
ATOM 3981 CD LYS H 68 33.794 24.057 28.427 1.00 29.68 B c
ATOM 3982 CE LYS H 68 35.058 24.267 29.243 1.00 29.46 B c
ATOM 3983 NZ LYS H 68 35.195 25.675 29.705 1.00 29.58 B N
ATOM 3984 C LYS H 68 34.543 19.202 29.509 1.00 28.60 B c
ATOM 3985 O LYS H 68 34.879 19.622 30.618 1.00 28.64 B o
ATOM 3986 N CYS H 69 34.618 17.912 29.162 1.00 28.09 B N
ATOM 3987 CA CYS H 69 35.404 16.889 29.895 1.00 27.63 B c
ATOM 3988 CB CYS H 69 34.502 15.694 30.287 1.00 27.07 B c
ATOM 3989 SG CYS H 69 34.515 14.237 29.134 1.00 28.01 B s
ATOM 3990 C CYS H 69 36.550 16.388 29.003 1.00 27.69 B c
ATOM 3991 O CYS H 69 36.474 16.529 27.785 1.00 27.41 B o
ATOM 3992 N ASN H 70 37.563 15.732 29.576 1.00 28.06 B N
ATOM 3993 CA ASN H 70 38.498 14.929 28.760 1.00 28.87 B c
ATOM 3994 CB ASN H 70 39.930 15.507 28.746 1.00 30.52 B c
ATOM 3995 CG ASN H 70 40.024 16.921 29.323 1.00 39.60 B c
ATOM 3996 OD1 ASN H 70 39.691 17.905 28.661 1.00 44.97 B o
ATOM 3997 ND2 ASN H 70 40.562 17.019 30.542 1.00 51.04 B N
ATOM 3998 C ASN H 70 38.528 13.423 29.067 1.00 26.97 B c
ATOM 3999 O ASN H 70 39.060 13.009 30.096 1.00 26.50 B o
ATOM 4000 N GLY H 71 38.111 12.611 28.096 1.00 25.46 B N
ATOM 4001 CA GLY H 71 38.117 11.148 28.237 1.00 23.67 B c ATOM 4002 C GLY H 71 39.357 10.485 27.657 1.00 22.81 B C
ATOM 4003 O GLY H 71 40.279 11.169 27.211 1.00 22.79 B o
ATOM 4004 N TH H 72 39.400 9.155 27.687 1.00 21.93 B N
ATOM 4005 CA TH H 72 40.517 8.418 27.100 1.00 21.30 B C
ATOM 4006 CB TH H 72 40.594 6.975 27.644 1.00 21.12 B c
ATOM 4007 OG1 THR H 72 39.700 6.131 26.909 1.00 19.87 B o
ATOM 4008 CG2 THR H 72 40.210 6.947 29.115 1.00 20.76 B c
ATOM 4009 C THR H 72 40.436 8.407 25.571 1.00 21.50 B c
ATOM 4010 O THR H 72 39.458 7.924 24.999 1.00 21.85 B o
ATOM 4011 N ASP H 73 41.391 9.077 24.927 1.00 21.43 B N
ATOM 4012 CA ASP H 73 41.246 9.509 23.534 1.00 21.46 B c
ATOM 4013 CB ASP H 73 41.137 8.304 22.598 1.00 21.69 B c
ATOM 4014 CG ASP H 73 40.965 8.708 21.150 1.00 22.46 B c
ATOM 4015 OD1 ASP H 73 40.678 9.896 20.894 1.00 23.01 B o
ATOM 4016 OD2 ASP H 73 41.102 7.835 20.269 1.00 23.09 B o
ATOM 4017 C ASP H 73 40.060 10.451 23.324 1.00 20.96 B c
ATOM 4018 O ASP H 73 38.909 10.066 23.530 1.00 20.61 B o
ATOM 4019 N ALA H 74 40.342 11.642 22.802 1.00 20.42 B N
ATOM 4020 CA ALA H 74 39.342 12.698 22.730 1.00 20.38 B c
ATOM 4021 CB ALA H 74 39.707 13.839 23.670 1.00 20.11 B c
ATOM 4022 C ALA H 74 39.133 13.223 21.310 1.00 20.45 B c
ATOM 4023 O ALA H 74 38.545 14.286 21.121 1.00 20.46 B o
ATOM 4024 N LYS H 75 39.659 12.513 20.318 1.00 20.67 B N
ATOM 4025 CA LYS H 75 39.416 12.887 18.929 1.00 20.99 B c
ATOM 4026 CB LYS H 75 40.195 11.977 17.978 1.00 21.20 B c
ATOM 4027 CG LYS H 75 41.704 12.110 18.091 1.00 22.02 B c
ATOM 4028 CD LYS H 75 42.349 10.782 18.451 1.00 23.66 B c
ATOM 4029 CE LYS H 75 43.483 10.971 19.447 1.00 24.93 B c
ATOM 4030 NZ LYS H 75 43.559 9.859 20.434 1.00 25.55 B N
ATOM 4031 C LYS H 75 37.925 12.790 18.645 1.00 20.92 B c
ATOM 4032 O LYS H 75 37.397 13.474 17.768 1.00 20.92 B o
ATOM 4033 N VAL H 76 37.265 11.904 19.382 1.00 20.63 B N
ATOM 4034 CA VAL H 76 35.813 11.844 19.414 1.00 20.36 B c
ATOM 4035 CB VAL H 76 35.326 10.521 20.029 1.00 20.25 B c
ATOM 4036 CGI VAL H 76 33.817 10.537 20.157 1.00 20.82 B c
ATOM 4037 CG2 VAL H 76 35.769 9.341 19.175 1.00 20.09 B c
ATOM 4038 C VAL H 76 35.234 13.006 20.213 1.00 20.29 B c
ATOM 4039 O VAL H 76 35.629 13.244 21.356 1.00 20.21 B o
ATOM 4040 N LYS H 77 34.284 13.715 19.613 1.00 20.17 B N
ATOM 4041 CA LYS H 77 33.726 14.916 20.224 1.00 20.17 B c
ATOM 4042 CB LYS H 77 34.593 16.136 19.904 1.00 20.62 B c
ATOM 4043 CG LYS H 77 35.797 16.307 20.825 1.00 23.31 B c
ATOM 4044 CD LYS H 77 36.952 16.989 20.103 1.00 26.74 B c
ATOM 4045 CE LYS H 77 38.196 17.046 20.971 1.00 28.32 B c
ATOM 4046 NZ LYS H 77 39.203 18.004 20.436 1.00 29.66 B N
ATOM 4047 C LYS H 77 32.294 15.141 19.759 1.00 19.45 B c
ATOM 4048 O LYS H 77 31.971 16.170 19.165 1.00 19.36 B o
ATOM 4049 N LEU H 78 31.441 14.162 20.033 1.00 18.70 B N
ATOM 4050 CA LEU H 78 30.155 14.056 19.365 1.00 17.98 B c
ATOM 4051 CB LEU H 78 29.356 12.892 19.945 1.00 17.72 B c
ATOM 4052 CG LEU H 78 30.168 11.596 20.034 1.00 17.51 B c
ATOM 4053 CD1 LEU H 78 29.321 10.446 20.554 1.00 17.41 B c
ATOM 4054 CD2 LEU H 78 30.802 11.249 18.690 1.00 17.62 B c
ATOM 4055 C LEU H 78 29.354 15.355 19.422 1.00 17.77 B c
ATOM 4056 O LEU H 78 28.996 15.911 18.384 1.00 17.89 B o
ATOM 4057 N ILE H 79 29.145 15.882 20.624 1.00 17.29 B N
ATOM 4058 CA ILE H 79 28.336 17.086 20.778 1.00 17.00 B c
ATOM 4059 CB ILE H 79 28.194 17.527 22.256 1.00 16.96 B c
ATOM 4060 CGI ILE H 79 27.588 16.401 23.098 1.00 17.21 B c
ATOM 4061 CD1 ILE H 79 27.086 16.855 24.459 1.00 17.51 B c ATOM 4062 CG2 ILE H 79 27.307 18.762 22.359 1.00 17.30 B C
ATOM 4063 C ILE H 79 28.854 18.238 19.911 1.00 16.83 B C
ATOM 4064 O ILE H 79 28.119 18.753 19.065 1.00 17.02 B i 0
ATOM 4065 N LYS H 80 30.124 18.571 19.800 1.00 16.55 B N
ATOM 4066 CA LYS H 80 30.366 19.684 18.841 1.00 16.38 B C
ATOM 4067 CB LYS H 80 31.861 20.021 18.833 1.00 16.73 B c
ATOM 4068 CG LYS H 80 32.255 21.150 17.895 1.00 17.99 B c
ATOM 4069 CD LYS H 80 32.343 22.475 18.640 1.00 20.71 B c
ATOM 4070 CE LYS H 80 32.566 23.632 17.681 1.00 22.92 B c
ATOM 4071 NZ LYS H 80 31.339 23.929 16.886 1.00 24.75 B N
ATOM 4072 C LYS H 80 29.884 19.466 17.349 1.00 15.79 B c
ATOM 4073 O LYS H 80 29.216 20.348 16.717 1.00 15.32 B o
ATOM 4074 N GLN H 81 30.177 18.286 16.806 1.00 15.48 B N
ATOM 4075 CA GLN H 81 29.878 17.961 15.401 1.00 15.33 B c
ATOM 4076 CB GLN H 81 30.465 16.593 15.049 1.00 15.70 B c
ATOM 4077 CG GLN H 81 31.870 16.364 15.565 1.00 17.88 B c
ATOM 4078 CD GLN H 81 32.301 14.917 15.435 1.00 20.46 B c
ATOM 4079 OE1 GLN H 81 31.670 14.133 14.730 1.00 21.59 B o
ATOM 4080 NE2 GLN H 81 33.378 14.554 16.123 1.00 20.26 B N
ATOM 4081 C GLN H 81 28.388 17.966 15.047 1.00 14.63 B c
ATOM 4082 O GLN H 81 27.972 18.429 13.962 1.00 14.60 B o
ATOM 4083 N GLU H 82 27.589 17.434 15.964 1.00 13.81 B N
ATOM 4084 CA GLU H 82 26.157 17.373 15.759 1.00 13.37 B c
ATOM 4085 CB GLU H 82 25.479 16.677 16.938 1.00 13.20 B c
ATOM 4086 CG GLU H 82 25.315 15.176 16.781 1.00 15.04 B c
ATOM 4087 CD GLU H 82 24.344 14.824 15.669 1.00 17.51 B c
ATOM 4088 OE1 GLU H 82 23.130 15.074 15.841 1.00 18.22 B o
ATOM 4089 OE2 GLU H 82 24.789 14.286 14.632 1.00 17.87 B o
ATOM 4090 C GLU H 82 25.650 18.794 15.638 1.00 12.99 B c
ATOM 4091 O GLU H 82 24.834 19.102 14.767 1.00 12.89 B o
ATOM 4092 N LEU H 83 26.174 19.677 16.482 1.00 12.89 B N
ATOM 4093 CA LEU H 83 25.727 21.057 16.454 1.00 13.08 B c
ATOM 4094 CB LEU H 83 26.419 21.865 17.552 1.00 13.26 B c
ATOM 4095 CG LEU H 83 26.057 21.498 18.994 1.00 14.18 B c
ATOM 4096 CD1 LEU H 83 26.535 22.566 19.968 1.00 15.11 B c
ATOM 4097 CD2 LEU H 83 24.558 21.282 19.117 1.00 14.79 B c
ATOM 4098 C LEU H 83 26.032 21.656 15.092 1.00 13.18 B c
ATOM 4099 O LEU H 83 25.150 22.261 14.459 1.00 13.05 B o
ATOM 4100 N ASP H 84 27.239 21.416 14.581 1.00 13.56 B N
ATOM 4101 CA ASP H 84 27.527 21.999 13.258 1.00 14.15 B c
ATOM 4102 CB ASP H 84 28.982 21.729 12.856 1.00 14.80 B c
ATOM 4103 CG ASP H 84 29.949 21.873 14.018 1.00 18.26 B c
ATOM 4104 OD1 ASP H 84 30.237 23.025 14.417 1.00 21.11 B o
ATOM 4105 OD2 ASP H 84 30.439 20.837 14.522 1.00 22.12 B o
ATOM 4106 C ASP H 84 26.572 21.490 12.150 1.00 13.56 B c
ATOM 4107 O ASP H 84 26.023 22.286 11.326 1.00 13.70 B o
ATOM 4108 N LYS H 85 26.328 20.180 12.146 1.00 12.87 B N
ATOM 4109 CA LYS H 85 25.458 19.616 11.106 1.00 12.31 B c
ATOM 4110 CB LYS H 85 25.412 18.090 11.210 1.00 12.41 B c
ATOM 4111 CG LYS H 85 24.611 17.417 10.110 1.00 12.26 B c
ATOM 4112 CD LYS H 85 24.213 16.002 10.506 1.00 12.72 B c
ATOM 4113 CE LYS H 85 23.359 16.018 11.762 1.00 14.40 B c
ATOM 4114 NZ LYS H 85 22.929 14.654 12.180 1.00 16.45 B N
ATOM 4115 C LYS H 85 24.038 20.192 11.202 1.00 11.85 B c
ATOM 4116 O LYS H 85 23.384 20.522 10.179 1.00 11.66 B o
ATOM 4117 N TY H 86 23.571 20.318 12.442 1.00 11.32 B N
ATOM 4118 CA TY H 86 22.232 20.825 12.683 1.00 11.07 B c
ATOM 4119 CB TY H 86 21.875 20.784 14.167 1.00 11.12 B c
ATOM 4120 CG TYR H 86 20.899 21.871 14.551 1.00 11.30 B c
ATOM 4121 CD1 TYR H 86 19.564 21.805 14.169 1.00 12.16 B c ATOM 4122 CE1 TY H 86 18.672 22.804 14.514 1.00 12.39 B C
ATOM 4123 CZ TYR H 86 19.106 23.886 15.243 1.00 12.62 B C
ATOM 4124 OH TYR H 86 18.218 24.880 15.587 1.00 12.72 B o
ATOM 4125 CE2 TYR H 86 20.428 23.980 15.632 1.00 11.38 B c
ATOM 4126 CD2 TYR H 86 21.315 22.979 15.284 1.00 11.05 B c
ATOM 4127 C TYR H 86 22.120 22.247 12.181 1.00 10.75 B c
ATOM 4128 O TYR H 86 21.114 22.622 11.573 1.00 10.45 B o
ATOM 4129 N LYS H 87 23.155 23.046 12.419 1.00 10.66 B N
ATOM 4130 CA LYS H 87 23.093 24.423 11.971 1.00 11.03 B c
ATOM 4131 CB LYS H 87 24.333 25.191 12.407 1.00 11.36 B c
ATOM 4132 CG LYS H 87 24.600 25.106 13.890 1.00 12.79 B c
ATOM 4133 CD LYS H 87 25.805 25.931 14.269 1.00 14.76 B c
ATOM 4134 CE LYS H 87 25.989 25.979 15.771 1.00 15.29 B c
ATOM 4135 NZ LYS H 87 27.137 26.849 16.138 1.00 16.27 B N
ATOM 4136 C LYS H 87 22.961 24.455 10.457 1.00 10.83 B c
ATOM 4137 O LYS H 87 22.122 25.189 9.920 1.00 11.11 B o
ATOM 4138 N ASN H 88 23.724 23.621 9.755 1.00 10.52 B N
ATOM 4139 CA ASN H 88 23.568 23.646 8.297 1.00 10.21 B c
ATOM 4140 CB ASN H 88 24.586 22.715 7.640 1.00 10.61 B c
ATOM 4141 CG ASN H 88 24.426 22.646 6.134 1.00 11.81 B c
ATOM 4142 OD1 ASN H 88 24.215 23.664 5.474 1.00 12.97 B o
ATOM 4143 ND2 ASN H 88 24.515 21.443 5.585 1.00 13.82 B N
ATOM 4144 C ASN H 88 22.142 23.279 7.825 1.00 9.42 B C
ATOM 4145 o ASN H 88 21.538 23.959 6.939 1.00 8.94 B o
ATOM 4146 N ALA H 89 21.576 22.237 8.435 1.00 8.77 B N
ATOM 4147 CA ALA H 89 20.225 21.834 8.022 1.00 8.21 B C
ATOM 4148 CB ALA H 89 19.811 20.551 8.725 1.00 7.99 B c
ATOM 4149 C ALA H 89 19.208 22.951 8.293 1.00 7.78 B c
ATOM 4150 o ALA H 89 18.307 23.249 7.472 1.00 7.88 B o
ATOM 4151 N VAL H 90 19.383 23.581 9.449 1.00 7.01 B N
ATOM 4152 CA VAL H 90 18.493 24.639 9.880 1.00 6.26 B c
ATOM 4153 CB VAL H 90 18.866 25.140 11.289 1.00 5.91 B c
ATOM 4154 CGI VAL H 90 18.089 26.401 11.626 1.00 5.92 B C
ATOM 4155 CG2 VAL H 90 18.608 24.054 12.318 1.00 5.26 B C
ATOM 4156 C VAL H 90 18.565 25.785 8.894 1.00 6.25 B C
ATOM 4157 O VAL H 90 17.547 26.368 8.538 1.00 6.32 B O
ATOM 4158 N THR H 91 19.771 26.092 8.434 1.00 6.24 B N
ATOM 4159 CA THR H 91 19.956 27.171 7.478 1.00 6.68 B C
ATOM 4160 CB THR H 91 21.444 27.375 7.139 1.00 6.62 B C
ATOM 4161 OG1 THR H 91 22.183 27.602 8.345 1.00 7.19 B O
ATOM 4162 CG2 THR H 91 21.619 28.565 6.210 1.00 7.27 B C
ATOM 4163 C THR H 91 19.203 26.886 6.180 1.00 7.02 B C
ATOM 4164 O THR H 91 18.505 27.767 5.661 1.00 7.16 B O
ATOM 4165 N GLU H 92 19.285 25.654 5.679 1.00 7.31 B N
ATOM 4166 CA GLU H 92 18.529 25.358 4.446 1.00 7.81 B C
ATOM 4167 CB GLU H 92 18.838 23.939 3.965 1.00 8.23 B C
ATOM 4168 CG GLU H 92 20.139 23.800 3.192 1.00 10.91 B C
ATOM 4169 CD GLU H 92 20.104 24.541 1.870 1.00 14.95 B C
ATOM 4170 OE1 GLU H 92 19.434 24.052 0.934 1.00 16.14 B O
ATOM 4171 OE2 GLU H 92 20.751 25.605 1.762 1.00 16.53 B O
ATOM 4172 C GLU H 92 17.003 25.530 4.644 1.00 7.47 B C
ATOM 4173 O GLU H 92 16.248 26.099 3.776 1.00 7.32 B O
ATOM 4174 N LEU H 93 16.541 25.053 5.800 1.00 7.30 B N
ATOM 4175 CA LEU H 93 15.117 25.171 6.098 1.00 7.47 B C
ATOM 4176 CB LEU H 93 14.760 24.426 7.385 1.00 7.15 B C
ATOM 4177 CG LEU H 93 14.797 22.898 7.297 1.00 7.20 B C
ATOM 4178 CD1 LEU H 93 14.346 22.282 8.610 1.00 7.93 B C
ATOM 4179 CD2 LEU H 93 13.941 22.397 6.141 1.00 6.91 B C
ATOM 4180 C LEU H 93 14.686 26.639 6.179 1.00 7.89 B C
ATOM 4181 O LEU H 93 13.626 27.012 5.675 1.00 7.94 B O ATOM 4182 N GLN H 94 15.527 27.464 6.797 1.00 8.31 B N
ATOM 4183 CA GLN H 94 15.259 28.893 6.952 1.00 9.05 B C
ATOM 4184 CB GLN H 94 16.325 29.554 7.831 1.00 9.18 B C
ATOM 4185 CG GLN H 94 16.331 29.049 9.271 1.00 10.79 B C
ATOM 4186 CD GLN H 94 17.231 29.868 10.179 1.00 13.82 B C
ATOM 4187 OE1 GLN H 94 17.866 30.828 9.741 1.00 14.98 B O
ATOM 4188 NE2 GLN H 94 17.289 29.493 11.452 1.00 15.25 B N
ATOM 4189 C GLN H 94 15.190 29.545 5.576 1.00 9.25 B C
ATOM 4190 O GLN H 94 14.389 30.446 5.329 1.00 9.43 B o
ATOM 4191 N LEU H 95 16.050 29.058 4.691 1.00 9.55 B N
ATOM 4192 CA LEU H 95 16.140 29.479 3.294 1.00 10.17 B C
ATOM 4193 CB LEU H 95 17.327 28.800 2.605 1.00 9.79 B c
ATOM 4194 CG LEU H 95 18.721 29.321 2.958 1.00 8.86 B c
ATOM 4195 CDl LEU H 95 19.789 28.548 2.198 1.00 8.31 B c
ATOM 4196 CD2 LEU H 95 18.823 30.809 2.667 1.00 7.62 B c
ATOM 4197 C LEU H 95 14.865 29.250 2.467 1.00 11.22 B c
ATOM 4198 O LEU H 95 14.579 30.030 1.560 1.00 11.55 B o
ATOM 4199 N LEU H 96 14.105 28.190 2.748 1.00 12.40 B N
ATOM 4200 CA LEU H 96 12.870 27.931 1.929 1.00 13.66 B c
ATOM 4201 CB LEU H 96 12.338 26.527 2.247 1.00 13.38 B c
ATOM 4202 CG LEU H 96 13.163 25.359 1.709 1.00 13.32 B c
ATOM 4203 CDl LEU H 96 12.554 24.028 2.122 1.00 12.84 B C
ATOM 4204 CD2 LEU H 96 13.281 25.453 0.197 1.00 13.38 B C
ATOM 4205 C LEU H 96 11.631 28.927 1.839 1.00 14.97 B C
ATOM 4206 O LEU H 96 10.836 28.843 0.903 1.00 15.21 B O
ATOM 4207 N MET H 97 11.500 29.832 2.808 1.00 16.74 B N
ATOM 4208 CA MET H 97 10.348 30.575 3.317 1.00 18.96 B C
ATOM 4209 CB MET H 97 10.619 31.113 4.726 1.00 19.12 B C
ATOM 4210 CG MET H 97 10.944 30.037 5.758 1.00 21.87 B C
ATOM 4211 SD MET H 97 9.537 28.994 6.201 1.00 27.46 B S
ATOM 4212 CE MET H 97 8.667 28.891 4.638 1.00 24.25 B C
ATOM 4213 C MET H 97 9.912 31.705 2.386 1.00 20.09 B C
ATOM 4214 O MET H 97 8.725 32.019 2.294 1.00 20.58 B O
ATOM 4215 N GLN H 98 10.867 32.274 1.658 1.00 21.33 B N
ATOM 4216 CA GLN H 98 10.593 33.429 0.809 1.00 22.21 B C
ATOM 4217 CB GLN H 98 11.279 34.679 1.364 1.00 22.53 B C
ATOM 4218 CG GLN H 98 11.165 34.831 2.872 1.00 23.85 B C
ATOM 4219 CD GLN H 98 12.329 34.200 3.612 1.00 25.21 B C
ATOM 4220 OE1 GLN H 98 12.539 32.989 3.544 1.00 24.47 B O
ATOM 4221 NE2 GLN H 98 13.058 35.012 4.369 1.00 24.85 B N
ATOM 4222 C GLN H 98 11.035 33.183 - 0.629 1.00 22.15 B C
ATOM 4223 O GLN H 98 11.448 32.080 - -0.982 1.00 21.77 B O
ATOM 4224 N PHE H 137 5.312 39.031 - 3.961 1.00 33.25 B N
ATOM 4225 CA PHE H 137 5.277 37.601 ■4.244 1.00 36.79 B C
ATOM 4226 CB PHE H 137 3.903 37.193 4.778 1.00 20.00 B C
ATOM 4227 CG PHE H 137 2.795 37.350 ■3.779 1.00 20.00 B C
ATOM 4228 CDl PHE H 137 2.542 36.360 -2.843 1.00 20.00 B C
ATOM 4229 CE1 PHE H 137 1.524 36.503 -1.920 1.00 20.00 B C
ATOM 4230 CZ PHE H 137 0.751 37.645 1.920 1.00 20.00 B C
ATOM 4231 CE2 PHE H 137 1.003 38.646 -2.836 1.00 20.00 B C
ATOM 4232 CD2 PHE H 137 2.015 38.493 -3.764 1.00 20.00 B C
ATOM 4233 C PHE H 137 6.359 37.207 -5.241 1.00 48.73 B C
ATOM 4234 O PHE H 137 6.595 36.022 -5.477 1.00 49.28 B O
ATOM 4235 N LEU H 138 6.975 38.204 -5.868 1.00 42.04 B N
ATOM 4236 CA LEU H 138 8.094 37.959 -6.768 1.00 44.26 B C
ATOM 4237 CB LEU H 138 8.582 39.268 -7.389 1.00 20.00 B C
ATOM 4238 CG LEU H 138 7.578 40.005 -8.278 1.00 20.00 B C
ATOM 4239 CDl LEU H 138 8.178 41.296 -8.816 1.00 20.00 B C
ATOM 4240 CD2 LEU H 138 7.101 39.112 -9.411 1.00 20.00 B C
ATOM 4241 C LEU H 138 9.234 37.274 -6.025 1.00 43.68 B C ATOM 4242 O LEU H 138 10.107 36.658 -6.636 1.00 50.27 B O
ATOM 4243 N GLY H 139 9.188 37.343 -4.698 1.00 38.56 B N
ATOM 4244 CA GLY H 139 10.191 36.699 -3.860 1.00 47.99 B C
ATOM 4245 C GLY H 139 10.260 35.202 -4.081 1.00 44.53 B C
ATOM 4246 O GLY H 139 11.284 34.575 -3.815 1.00 32.21 B o
ATOM 4247 N PHE H 140 9.173 34.630 - 4.590 1.00 46.33 B N
ATOM 4248 CA PHE H 140 9.070 33.183 -4.735 1.00 42.95 B C
ATOM 4249 CB PHE H 140 7.618 32.723 -4.576 1.00 20.00 B c
ATOM 4250 CG PHE H 140 7.058 32.941 -3.201 1.00 20.00 B c
ATOM 4251 CD1 PHE H 140 7.285 32.021 -2.190 1.00 20.00 B c
ATOM 4252 CE1 PHE H 140 6.763 32.217 -0.926 1.00 20.00 B c
ATOM 4253 CZ PHE H 140 5.992 33.332 -0.664 1.00 20.00 B c
ATOM 4254 CE2 PHE H 140 5.747 34.249 -1.667 1.00 20.00 B c
ATOM 4255 CD2 PHE H 140 6.271 34.047 -2.929 1.00 20.00 B c
ATOM 4256 C PHE H 140 9.632 32.695 - 6.071 1.00 38.13 B c
ATOM 4257 O PHE H 140 9.693 31.490 - 6.322 1.00 57.33 B o
ATOM 4258 N LEU H 141 10.017 33.631 -6.934 1.00 35.20 B N
ATOM 4259 CA LEU H 141 10.453 33.294 -8.288 1.00 27.01 B c
ATOM 4260 CB LEU H 141 11.557 32.235 -8.254 1.00 20.00 B c
ATOM 4261 CG LEU H 141 12.886 32.672 -7.636 1.00 20.00 B c
ATOM 4262 CD1 LEU H 141 13.836 31.493 -7.513 1.00 20.00 B c
ATOM 4263 CD2 LEU H 141 13.520 33.794 -8.445 1.00 20.00 B c
ATOM 4264 C LEU H 141 9.287 32.812 - 9.144 1.00 35.79 B c
ATOM 4265 O LEU H 141 8.355 33.567 - ■9.417 1.00 46.92 B o
ATOM 4266 N LEU H 142 9.342 31.555 - ■9.570 1.00 38.67 B N
ATOM 4267 CA LEU H 142 8.195 30.927 -10.207 1.00 33.84 B c
ATOM 4268 CB LEU H 142 8.610 30.262 -11.517 1.00 20.00 B c
ATOM 4269 CG LEU H 142 9.069 31.205 -12.629 1.00 20.00 B c
ATOM 4270 CD1 LEU H 142 9.474 30.415 -13.865 1.00 20.00 B c
ATOM 4271 CD2 LEU H 142 7.974 32.209 -12.964 1.00 20.00 B c
ATOM 4272 C LEU H 142 7.541 29.910 - 9.278 1.00 36.89 B c
ATOM 4273 O LEU H 142 8.215 29.038 - ■8.729 1.00 45.42 B o
ATOM 4274 N GLY H 143 6.268 30.132 -8.975 1.00 26.84 B N
ATOM 4275 CA GLY H 143 5.577 29.350 -7.958 1.00 27.41 B c
ATOM 4276 C GLY H 143 4.243 28.849 ■ -8.463 1.00 29.08 B c
ATOM 4277 O GLY H 143 3.592 29.504 -9.277 1.00 40.24 B o
ATOM 4278 N VAL H 144 3.848 27.665 -8.010 1.00 30.17 B N
ATOM 4279 CA VAL H 144 2.550 27.121 -8.373 1.00 34.15 B c
ATOM 4280 CB VAL H 144 2.497 25.596 -8.195 1.00 20.00 B c
ATOM 4281 CGI VAL H 144 1.073 25.102 , -8.370 1.00 20.00 B c
ATOM 4282 CG2 VAL H 144 3.426 24.913 -9.187 1.00 20.00 B c
ATOM 4283 C VAL H 144 1.449 27.759 ■ -7.538 1.00 36.67 B c
ATOM 4284 O VAL H 144 1.723 28.490 -6.587 1.00 42.49 B o
ATOM 4285 N GLY H 145 0.204 27.526 -7.938 1.00 47.09 B N
ATOM 4286 CA GLY H 145 -0.946 27.979 -7.166 1.00 44.51 B c
ATOM 4287 C GLY H 145 -0.857 27.562 -5.712 1.00 44.94 B c
ATOM 4288 O GLY H 145 -1.097 28.365 -4.810 1.00 40.58 B o
ATOM 4289 N SE H 146 -0.529 26.297 - 5.473 1.00 42.06 B N
ATOM 4290 CA SEPv H 146 -0.433 25.788 -4.109 1.00 47.39 B c
ATOM 4291 CB SEPv H 146 -0.198 24.275 -4.119 1.00 20.00 B c
ATOM 4292 OG SEPv H 146 1.004 23.951 -4.796 1.00 20.00 B o
ATOM 4293 C SEPv H 146 0.665 26.482 - 3.307 1.00 51.48 B c
ATOM 4294 O SEPv H 146 0.481 26.809 - 2.131 1.00 47.45 B o
ATOM 4295 N ALA H 147 1.807 26.710 -3.949 1.00 39.51 B N
ATOM 4296 CA ALA H 147 2.943 27.334 -3.282 1.00 43.38 B c
ATOM 4297 CB ALA H 147 4.162 27.326 -4.194 1.00 20.00 B c
ATOM 4298 C ALA H 147 2.633 28.754■ -2.821 1.00 47.39 B c
ATOM 4299 O ALA H 147 2.997 29.147 -1.713 1.00 50.18 B o
ATOM 4300 N ILE H 148 1.952 29.520 -3.668 1.00 44.67 B N
ATOM 4301 CA ILE H 148 1.602 30.892 - -3.323 1.00 43.56 B c ATOM 4302 CB ILE H 148 0.921 31.615 -4.499 1.00 20.00 B C
ATOM 4303 CGI ILE H 148 1.854 31.657 -5.711 1.00 20.00 B C
ATOM 4304 CD 1 ILE H 148 1.259 32.353 -6.916 1.00 20.00 B c
ATOM 4305 CG2 ILE H 148 0.504 33.020 -4.092 1.00 20.00 B c
ATOM 4306 C ILE H 148 0.672 30.913 -2.117 1.00 51.18 B c
ATOM 4307 O ILE H 148 0.830 31.730 -1.208 1.00 39.17 B o
ATOM 4308 N ALA H 149 -0.289 29.995 -2.109 1.00 42.17 B N
ATOM 4309 CA ALA H 149 -1.233 29.895 -1.007 1.00 36.76 B C
ATOM 4310 CB ALA H 149 -2.297 28.854 -1.312 1.00 20.00 B C
ATOM 4311 C ALA H 149 -0.490 29.541 0.272 1.00 45.19 B C
ATOM 4312 O ALA H 149 -0.771 30.090 1.340 1.00 47.83 B O
ATOM 4313 N SE H 150 0.471 28.630 0.157 1.00 43.64 B N
ATOM 4314 CA SE H 150 1.250 28.218 1.315 1.00 43.46 B C
ATOM 4315 CB SER H 150 2.211 27.088 0.943 1.00 20.00 B C
ATOM 4316 OG SER H 150 3.113 27.499 -0.069 1.00 20.00 B O
ATOM 4317 C SER H 150 2.024 29.408 1.865 1.00 44.80 B C
ATOM 4318 O SER H 150 2.095 29.610 3.077 1.00 41.55 B O
ATOM 4319 N GLY H 151 2.590 30.205 0.964 1.00 27.01 B N
ATOM 4320 CA GLY H 151 3.342 31.379 1.362 1.00 35.21 B C
ATOM 4321 C GLY H 151 2.454 32.375 2.078 1.00 42.40 B C
ATOM 4322 O GLY H 151 2.849 32.969 3.083 1.00 45.11 B O
ATOM 4323 N VAL H 152 1.241 32.551 1.563 1.00 40.20 B N
ATOM 4324 CA VAL H 152 0.293 33.471 2.174 1.00 46.73 B C
ATOM 4325 CB VAL H 152 -1.000 33.585 1.346 1.00 20.00 B C
ATOM 4326 CGI VAL H 152 -1.970 34.551 2.009 1.00 20.00 B C
ATOM 4327 CG2 VAL H 152 -0.682 34.029 -0.073 1.00 20.00 B C
ATOM 4328 C VAL H 152 -0.052 32.995 3.579 1.00 48.62 B C
ATOM 4329 O VAL H 152 -0.133 33.792 4.517 1.00 49.32 B O
ATOM 4330 N ALA H 153 -0.239 31.686 3.722 1.00 35.09 B N
ATOM 4331 CA ALA H 153 -0.567 31.112 5.018 1.00 42.37 B C
ATOM 4332 CB ALA H 153 -0.849 29.625 4.885 1.00 20.00 B C
ATOM 4333 C ALA H 153 0.578 31.353 5.992 1.00 37.79 B C
ATOM 4334 O ALA H 153 0.359 31.696 7.154 1.00 39.25 B O
ATOM 4335 N VAL H 154 1.802 31.189 5.502 1.00 38.88 B N
ATOM 4336 CA VAL H 154 2.982 31.394 6.328 1.00 35.53 B C
ATOM 4337 CB VAL H 154 4.274 31.042 5.568 1.00 20.00 B C
ATOM 4338 CGI VAL H 154 5.489 31.267 6.454 1.00 20.00 B C
ATOM 4339 CG2 VAL H 154 4.223 29.605 5.074 1.00 20.00 B C
ATOM 4340 C VAL H 154 3.053 32.842 6.791 1.00 41.00 B C
ATOM 4341 O VAL H 154 3.380 33.118 7.945 1.00 50.08 B o
ATOM 4342 N SER H 155 2.742 33.766 5.888 1.00 37.82 B N
ATOM 4343 CA SER H 155 2.753 35.181 6.232 1.00 44.68 B C
ATOM 4344 CB SER H 155 2.496 36.038 4.991 1.00 20.00 B c
ATOM 4345 OG SER H 155 1.238 35.736 4.414 1.00 20.00 B o
ATOM 4346 C SER H 155 1.706 35.477 7.300 1.00 41.82 B c
ATOM 4347 O SER H 155 1.960 36.224 8.245 1.00 49.37 B o
ATOM 4348 N LYS H 156 0.528 34.880 7.144 1.00 36.99 B N
ATOM 4349 CA LYS H 156 -0.559 35.059 8.102 1.00 35.11 B c
ATOM 4350 CB LYS H 156 -1.843 34.411 7.579 1.00 20.00 B c
ATOM 4351 CG LYS H 156 -2.334 34.983 6.259 1.00 20.00 B c
ATOM 4352 CD LYS H 156 -3.611 34.297 5.801 1.00 20.00 B c
ATOM 4353 CE LYS H 156 -4.102 34.869 4.481 1.00 20.00 B c
ATOM 4354 NZ LYS H 156 -5.353 34.206 4.020 1.00 20.00 B N
ATOM 4355 C LYS H 156 -0.210 34.493 9.476 1.00 35.98 B c
ATOM 4356 O LYS H 156 -0.535 35.081 10.507 1.00 42.31 B o
ATOM 4357 N VAL H 157 0.448 33.339 9.470 1.00 37.88 B N
ATOM 4358 CA VAL H 157 0.794 32.617 10.689 1.00 50.94 B C
ATOM 4359 CB VAL H 157 1.143 31.145 10.396 1.00 20.00 B C
ATOM 4360 CGI VAL H 157 1.572 30.439 11.672 1.00 20.00 B C
ATOM 4361 CG2 VAL H 157 -0.043 30.435 9.762 1.00 20.00 B C ATOM 4362 C VAL H 157 1.962 33.277 11.415 1.00 47.82 B C
ATOM 4363 O VAL H 157 2.296 32.905 12.541 1.00 56.87 B o
ATOM 4364 N LEU H 158 2.533 34.304 10.794 1.00 39.52 B N
ATOM 4365 CA LEU H 158 3.727 34.956 11.320 1.00 50.27 B C
ATOM 4366 CB LEU H 158 4.080 36.188 10.484 1.00 20.00 B c
ATOM 4367 CG LEU H 158 4.493 35.927 9.034 1.00 20.00 B c
ATOM 4368 CD1 LEU H 158 4.688 37.237 8.287 1.00 20.00 B c
ATOM 4369 CD2 LEU H 158 5.754 35.079 8.976 1.00 20.00 B c
ATOM 4370 C LEU H 158 3.589 35.334 12.794 1.00 54.47 B c
ATOM 4371 O LEU H 158 4.512 35.127 13.582 1.00 49.26 B o
ATOM 4372 N HIS H 159 2.448 35.754 13.309 1.00 59.45 B N
ATOM 4373 CA HIS H 159 2.473 36.028 14.762 1.00 49.11 B c
ATOM 4374 CB HIS H 159 1.136 36.614 15.221 1.00 20.00 B c
ATOM 4375 CG HIS H 159 0.780 37.903 14.548 1.00 20.00 B c
ATOM 4376 ND1 HIS H 159 1.149 39.132 15.051 1.00 20.00 B N
ATOM 4377 CE1 HIS H 159 0.699 40.085 14.254 1.00 20.00 B c
ATOM 4378 NE2 HIS H 159 0.052 39.519 13.252 1.00 20.00 B N
ATOM 4379 CD2 HIS H 159 0.087 38.155 13.412 1.00 20.00 B C
ATOM 4380 C HIS H 159 2.830 34.775 15.616 1.00 44.09 B C
ATOM 4381 O HIS H 159 3.627 34.822 16.600 1.00 42.13 B 1 □
ATOM 4382 N LEU H 160 2.261 33.646 15.207 1.00 37.55 B N
ATOM 4383 CA LEU H 160 2.402 32.391 15.934 1.00 43.52 B C
ATOM 4384 CB LEU H 160 1.521 31.310 15.302 1.00 20.00 B C
ATOM 4385 CG LEU H 160 0.018 31.596 15.268 1.00 20.00 B c
ATOM 4386 CD1 LEU H 160 -0.734 30.443 14.620 1.00 20.00 B c
ATOM 4387 CD2 LEU H 160 -0.509 31.865 16.668 1.00 20.00 B c
ATOM 4388 C LEU H 160 3.839 31.887 16.044 1.00 47.22 B c
ATOM 4389 O LEU H 160 4.233 31.383 17.091 1.00 43.25 B o
ATOM 4390 N GLU H 161 4.620 32.011 14.976 1.00 40.88 B N
ATOM 4391 CA GLU H 161 5.996 31.524 15.008 1.00 40.61 B c
ATOM 4392 CB GLU H 161 6.644 31.658 13.628 1.00 20.00 B c
ATOM 4393 CG GLU H 161 5.936 30.878 12.532 1.00 20.00 B c
ATOM 4394 CD GLU H 161 6.606 31.031 11.181 1.00 20.00 B c
ATOM 4395 OE1 GLU H 161 6.113 30.437 10.200 1.00 20.00 B o
ATOM 4396 OE2 GLU H 161 7.628 31.745 11.101 1.00 20.00 B o
ATOM 4397 C GLU H 161 6.833 32.259 16.054 1.00 39.76 B c
ATOM 4398 O GLU H 161 7.606 31.642 16.795 1.00 44.02 B o
ATOM 4399 N GLY H 162 6.679 33.566 16.211 1.00 34.18 B N
ATOM 4400 CA GLY H 162 7.497 34.204 17.230 1.00 35.01 B c
ATOM 4401 C GLY H 162 7.170 33.593 18.586 1.00 34.86 B c
ATOM 4402 O GLY H 162 8.065 33.226 19.372 1.00 47.81 B o
ATOM 4403 N GLU H 163 5.875 33.431 18.838 1.00 40.78 B N
ATOM 4404 CA GLU H 163 5.403 32.797 20.058 1.00 37.20 B c
ATOM 4405 CB GLU H 163 3.877 32.847 20.137 1.00 20.00 B c
ATOM 4406 CG GLU H 163 3.301 34.254 20.134 1.00 20.00 B c
ATOM 4407 CD GLU H 163 1.788 34.264 20.214 1.00 20.00 B c
ATOM 4408 OE1 GLU H 163 1.199 35.365 20.219 1.00 20.00 B o
ATOM 4409 OE2 GLU H 163 1.186 33.171 20.273 1.00 20.00 B o
ATOM 4410 C GLU H 163 5.884 31.355 20.065 1.00 46.12 B c
ATOM 4411 O GLU H 163 6.295 30.824 21.098 1.00 58.66 B o
ATOM 4412 N VAL H 164 5.832 30.731 18.893 1.00 42.23 B N
ATOM 4413 CA VAL H 164 6.270 29.353 18.740 1.00 35.45 B c
ATOM 4414 CB VAL H 164 6.021 28.836 17.311 1.00 20.00 B c
ATOM 4415 CGI VAL H 164 6.488 27.394 17.181 1.00 20.00 B c
ATOM 4416 CG2 VAL H 164 4.549 28.962 16.951 1.00 20.00 B c
ATOM 4417 C VAL H 164 7.753 29.241 19.061 1.00 46.32 B c
ATOM 4418 O VAL H 164 8.180 28.290 19.709 1.00 45.08 B o
ATOM 4419 N ASN H 165 8.536 30.217 18.611 1.00 40.82 B N
ATOM 4420 CA ASN H 165 9.966 30.227 18.891 1.00 46.48 B c
ATOM 4421 CB ASN H 165 10.653 31.372 18.145 1.00 20.00 B c ATOM 4422 CG ASN H 165 10.488 31.270 16.642 1.00 20.00 B C
ATOM 4423 OD1 ASN H 165 10.982 32.113 15.893 1.00 20.00 B O
ATOM 4424 ND2 ASN H 165 9.792 30.232 16.192 1.00 20.00 B N
ATOM 4425 C ASN H 165 10.227 30.342 20.389 1.00 50.90 B C
ATOM 4426 O ASN H 165 11.099 29.655 20.941 1.00 47.11 B O
ATOM 4427 N LYS H 166 9.453 31.198 21.052 1.00 48.36 B N
ATOM 4428 CA LYS H 166 9.605 31.351 22.495 1.00 38.71 B C
ATOM 4429 CB LYS H 166 8.692 32.461 23.019 1.00 20.00 B C
ATOM 4430 CG LYS H 166 8.968 33.828 22.414 1.00 20.00 B C
ATOM 4431 CD LYS H 166 8.030 34.881 22.980 1.00 20.00 B C
ATOM 4432 CE LYS H 166 8.306 36.249 22.376 1.00 20.00 B C
ATOM 4433 NZ LYS H 166 7.396 37.292 22.923 1.00 20.00 B N
ATOM 4434 C LYS H 166 9.284 30.029 23.192 1.00 45.07 B C
ATOM 4435 O LYS H 166 9.977 29.609 24.131 1.00 56.09 B O
ATOM 4436 N ILE H 167 8.238 29.366 22.709 1.00 42.02 B N
ATOM 4437 CA ILE H 167 7.817 28.091 23.272 1.00 43.86 B C
ATOM 4438 CB ILE H 167 6.527 27.577 22.607 1.00 20.00 B C
ATOM 4439 CGI ILE H 167 5.388 28.580 22.807 1.00 20.00 B C
ATOM 4440 CD 1 ILE H 167 4.079 28.150 22.181 1.00 20.00 B C
ATOM 4441 CG2 ILE H 167 6.147 26.214 23.164 1.00 20.00 B C
ATOM 4442 C ILE H 167 8.916 27.053 23.099 1.00 49.02 B C
ATOM 4443 O ILE H 167 9.178 26.260 23.998 1.00 37.71 B O
ATOM 4444 N LYS H 168 9.557 27.068 21.935 1.00 33.87 B N
ATOM 4445 CA LYS H 168 10.644 26.146 21.640 1.00 35.11 B C
ATOM 4446 CB LYS H 168 11.103 26.304 20.189 1.00 20.00 B C
ATOM 4447 CG LYS H 168 10.014 26.040 19.162 1.00 20.00 B C
ATOM 4448 CD LYS H 168 10.535 26.220 17.746 1.00 20.00 B C
ATOM 4449 CE LYS H 168 9.445 25.959 16.719 1.00 20.00 B C
ATOM 4450 NZ LYS H 168 9.941 26.134 15.326 1.00 20.00 B N
ATOM 4451 C LYS H 168 11.813 26.380 22.588 1.00 39.27 B C
ATOM 4452 O LYS H 168 12.422 25.429 23.078 1.00 32.39 B O
ATOM 4453 N SE H 169 12.121 27.647 22.854 1.00 41.30 B N
ATOM 4454 CA SER H 169 13.203 27.963 23.783 1.00 43.23 B C
ATOM 4455 CB SER H 169 13.446 29.472 23.832 1.00 20.00 B C
ATOM 4456 OG SER H 169 12.284 30.162 24.259 1.00 20.00 B O
ATOM 4457 C SER H 169 12.865 27.436 25.178 1.00 41.44 B C
ATOM 4458 O SER H 169 13.723 26.871 25.883 1.00 44.82 B O
ATOM 4459 N ALA H 170 11.604 27.605 25.566 1.00 39.78 B N
ATOM 4460 CA ALA H 170 11.161 27.131 26.870 1.00 41.01 B C
ATOM 4461 CB ALA H 170 9.720 27.541 27.124 1.00 20.00 B C
ATOM 4462 C ALA H 170 11.308 25.615 26.948 1.00 46.04 B C
ATOM 4463 O ALA H 170 11.743 25.072 27.964 1.00 46.67 B O
ATOM 4464 N LEU H 171 10.955 24.940 25.859 1.00 34.26 B N
ATOM 4465 CA LEU H 171 11.050 23.489 25.782 1.00 37.69 B C
ATOM 4466 CB LEU H 171 10.458 22.982 24.466 1.00 20.00 B C
ATOM 4467 CG LEU H 171 8.984 23.305 24.216 1.00 20.00 B C
ATOM 4468 CD1 LEU H 171 8.529 22.743 22.878 1.00 20.00 B C
ATOM 4469 CD2 LEU H 171 8.118 22.773 25.348 1.00 20.00 B C
ATOM 4470 C LEU H 171 12.499 23.044 25.912 1.00 44.67 B C
ATOM 4471 O LEU H 171 12.797 22.054 26.579 1.00 34.27 B O
ATOM 4472 N LEU H 172 13.400 23.783 25.272 1.00 34.80 B N
ATOM 4473 CA LEU H 172 14.817 23.464 25.344 1.00 28.87 B C
ATOM 4474 CB LEU H 172 15.626 24.402 24.447 1.00 20.00 B C
ATOM 4475 CG LEU H 172 15.281 24.379 22.956 1.00 20.00 B C
ATOM 4476 CD 1 LEU H 172 16.158 25.355 22.186 1.00 20.00 B C
ATOM 4477 CD2 LEU H 172 15.416 22.972 22.395 1.00 20.00 B C
ATOM 4478 C LEU H 172 15.291 23.577 26.786 1.00 29.90 B C
ATOM 4479 O LEU H 172 16.022 22.714 27.272 1.00 41.09 B O
ATOM 4480 N SER H 173 14.862 24.629 27.480 1.00 35.08 B N
ATOM 4481 CA SER H 173 15.184 24.754 28.902 1.00 35.53 B C ATOM 4482 CB SE H 173 14.727 26.109 29.442 1.00 20.00 B C
ATOM 4483 OG SER H 173 13.328 26.272 29.294 1.00 20.00 B o
ATOM 4484 C SER H 173 14.506 23.618 29.673 1.00 35.07 B c
ATOM 4485 O SER H 173 15.056 23.037 30.609 1.00 51.28 B o
ATOM 4486 N THR H 174 13.286 23.341 29.234 1.00 46.35 B N
ATOM 4487 CA THR H 174 12.335 22.383 29.786 1.00 43.83 B c
ATOM 4488 CB THR H 174 10.885 22.764 29.429 1.00 20.00 B c
ATOM 4489 OG1 THR H 174 10.725 22.762 28.004 1.00 20.00 E ; o
ATOM 4490 CG2 THR H 174 10.547 24.144 29.971 1.00 20.00 B , c
ATOM 4491 C THR H 174 12.616 20.979 29.263 1.00 52.54 B c
ATOM 4492 O THR H 174 12.523 20.726 28.063 1.00 64.10 B o
ATOM 4493 N ASN H 175 12.974 20.071 30.165 1.00 55.57 B N
ATOM 4494 CA ASN H 175 13.072 18.660 29.817 1.00 40.58 B c
ATOM 4495 CB ASN H 175 13.942 17.915 30.831 1.00 20.00 B c
ATOM 4496 CG ASN H 175 15.405 18.303 30.740 1.00 20.00 B c
ATOM 4497 OD1 ASN H 175 15.868 18.788 29.708 1.00 20.00 E ; o
ATOM 4498 ND2 ASN H 175 16.139 18.099 31.827 1.00 20.00 E ; N
ATOM 4499 C ASN H 175 11.695 18.009 29.714 1.00 43.65 B c
ATOM 4500 O ASN H 175 10.972 17.912 30.705 1.00 53.11 B o
ATOM 4501 N LYS H 176 11.296 17.666 28.491 1.00 44.89 B N
ATOM 4502 CA LYS H 176 9.986 17.068 28.250 1.00 46.42 B C
ATOM 4503 CB LYS H 176 8.873 18.052 28.618 1.00 20.00 B c
ATOM 4504 CG LYS H 176 8.873 18.468 30.088 1.00 20.00 B c
ATOM 4505 CD LYS H 176 7.844 19.557 30.362 1.00 20.00 B c
ATOM 4506 CE LYS H 176 7.773 19.904 31.841 1.00 20.00 B c
ATOM 4507 NZ LYS H 176 6.701 20.899 32.121 1.00 20.00 B N
ATOM 4508 C LYS H 176 9.829 16.596 26.806 1.00 45.00 B c
ATOM 4509 O LYS H 176 10.272 17.264 25.871 1.00 60.64 B o
ATOM 4510 N ALA H 177 9.245 15.415 26.634 1.00 46.01 B N
ATOM 4511 CA ALA H 177 8.914 14.913 25.306 1.00 43.65 B c
ATOM 4512 CB ALA H 177 8.530 13.442 25.374 1.00 20.00 B c
ATOM 4513 C ALA H 177 7.789 15.731 24.686 1.00 41.42 B c
ATOM 4514 O ALA H 177 7.894 16.184 23.547 1.00 45.37 B o
ATOM 4515 N VAL H 178 6.736 15.960 25.463 1.00 35.70 B N
ATOM 4516 CA VAL H 178 5.642 16.820 25.037 1.00 43.93 B c
ATOM 4517 CB VAL H 178 4.383 15.999 24.710 1.00 20.00 B c
ATOM 4518 CGI VAL H 178 3.229 16.919 24.341 1.00 20.00 B c
ATOM 4519 CG2 VAL H 178 4.672 15.014 23.585 1.00 20.00 B c
ATOM 4520 C VAL H 178 5.313 17.836 26.124 1.00 34.16 B c
ATOM 4521 O VAL H 178 5.395 17.527 27.311 1.00 44.45 B o
ATOM 4522 N VAL H 179 5.028 19.069 25.717 1.00 44.87 B N
ATOM 4523 CA VAL H 179 4.818 20.155 26.667 1.00 38.47 B c
ATOM 4524 CB VAL H 179 6.150 20.766 27.131 1.00 20.00 B c
ATOM 4525 CGI VAL H 179 5.908 21.808 28.221 1.00 20.00 B c
ATOM 4526 CG2 VAL H 179 7.097 19.678 27.609 1.00 20.00 B c
ATOM 4527 C VAL H 179 3.967 21.265 26.070 1.00 44.79 B c
ATOM 4528 O VAL H 179 4.226 21.727 24.959 1.00 51.88 B o
ATOM 4529 N SER H 180 3.025 21.765 26.862 1.00 45.23 B N
ATOM 4530 CA SER H 180 2.226 22.915 26.463 1.00 48.99 B c
ATOM 4531 CB SER H 180 0.976 23.033 27.340 1.00 20.00 B c
ATOM 4532 OG SER H 180 1.321 23.322 28.683 1.00 20.00 B o
ATOM 4533 C SER H 180 3.047 24.198 26.532 1.00 48.15 B c
ATOM 4534 O SER H 180 3.568 24.553 27.589 1.00 60.42 B o
ATOM 4535 N LEU H 181 3.261 24.821 25.378 1.00 42.42 B N
ATOM 4536 CA LEU H 181 3.872 26.143 25.325 1.00 43.22 B c
ATOM 4537 CB LEU H 181 4.252 26.498 23.888 1.00 20.00 B c
ATOM 4538 CG LEU H 181 5.279 25.577 23.233 1.00 20.00 B c
ATOM 4539 CD1 LEU H 181 5.583 26.043 21.818 1.00 20.00 B c
ATOM 4540 CD2 LEU H 181 6.541 25.519 24.073 1.00 20.00 B c
ATOM 4541 C LEU H 181 2.929 27.199 25.884 1.00 29.14 B c ATOM 4542 O LEU H 181 1.891 27.494 25.291 1.00 43.42 B O
ATOM 4543 N SE H 182 3.271 27.735 27.051 1.00 41.83 B N
ATOM 4544 CA SER H 182 2.365 28.619 27.770 1.00 53.52 B C
ATOM 4545 CB SER H 182 2.034 28.053 29.152 1.00 20.00 B C
ATOM 4546 OG SER H 182 3.184 28.019 29.978 1.00 20.00 B o
ATOM 4547 C SER H 182 2.914 30.036 27.891 1.00 44.76 B c
ATOM 4548 O SER H 182 4.095 30.236 28.178 1.00 37.73 B o
ATOM 4549 N ASN H 183 2.072 31.008 27.556 1.00 47.84 B N
ATOM 4550 CA ASN H 183 2.258 32.384 27.996 1.00 59.45 B c
ATOM 4551 CB ASN H 183 2.304 33.316 26.782 1.00 20.00 B c
ATOM 4552 CG ASN H 183 3.512 33.066 25.897 1.00 20.00 B c
ATOM 4553 OD1 ASN H 183 4.574 32.671 26.379 1.00 20.00 B o
ATOM 4554 ND2 ASN H 183 3.384 33.386 24.615 1.00 20.00 B N
ATOM 4555 C ASN H 183 1.117 32.791 28.924 1.00 75.41 B c
ATOM 4556 O ASN H 183 -0.008 32.318 28.769 1.00102.31 B o
ATOM 4557 N GLY H 184 1.432 33.563 29.959 1.00 79.30 B N
ATOM 4558 CA GLY H 184 0.435 33.947 30.957 1.00 88.92 B c
ATOM 4559 C GLY H 184 -0.954 33.397 30.674 1.00101.85 B c
ATOM 4560 O GLY H 184 -1.760 34.037 29.999 1.00113.48 B o
ATOM 4561 N VAL H 185 -1.218 32.190 31.167 1.00 86.84 B N
ATOM 4562 CA VAL H 185 -2.573 31.636 31.236 1.00 81.80 B c
ATOM 4563 CB VAL H 185 -3.558 32.579 31.958 1.00 20.00 B c
ATOM 4564 CGI VAL H 185 -4.974 32.022 31.887 1.00 20.00 B c
ATOM 4565 CG2 VAL H 185 -3.135 32.783 33.405 1.00 20.00 B c
ATOM 4566 C VAL H 185 -3.164 31.228 29.887 1.00 81.69 B c
ATOM 4567 O VAL H 185 -4.347 30.900 29.801 1.00 99.84 B o
ATOM 4568 N SER H 186 -2.336 31.193 28.848 1.00 70.63 B N
ATOM 4569 CA SER H 186 -2.819 30.830 27.519 1.00 72.29 B c
ATOM 4570 CB SER H 186 -3.084 32.081 26.679 1.00 20.00 B c
ATOM 4571 OG SER H 186 -1.884 32.787 26.420 1.00 20.00 B o
ATOM 4572 C SER H 186 -1.865 29.891 26.789 1.00 62.99 B c
ATOM 4573 O SER H 186 -0.655 30.115 26.765 1.00 58.35 B o
ATOM 4574 N VAL H 187 -2.422 28.851 26.177 1.00 66.49 B N
ATOM 4575 CA VAL H 187 -1.627 27.877 25.438 1.00 57.36 B c
ATOM 4576 CB VAL H 187 -2.284 26.484 25.457 1.00 20.00 B c
ATOM 4577 CGI VAL H 187 -1.504 25.516 24.583 1.00 20.00 B c
ATOM 4578 CG2 VAL H 187 -2.383 25.963 26.883 1.00 20.00 B c
ATOM 4579 C VAL H 187 -1.432 28.317 23.991 1.00 53.67 B c
ATOM 4580 O VAL H 187 -2.401 28.531 23.262 1.00 50.10 B o
ATOM 4581 N LEU H 188 -0.176 28.476 23.588 1.00 43.20 B N
ATOM 4582 CA LEU H 188 0.143 28.854 22.217 1.00 41.76 B c
ATOM 4583 CB LEU H 188 1.487 29.581 22.160 1.00 20.00 B c
ATOM 4584 CG LEU H 188 1.549 30.938 22.862 1.00 20.00 B c
ATOM 4585 CD1 LEU H 188 2.957 31.507 22.799 1.00 20.00 B c
ATOM 4586 CD2 LEU H 188 0.548 31.907 22.250 1.00 20.00 B c
ATOM 4587 C LEU H 188 0.166 27.634 21.304 1.00 44.75 B c
ATOM 4588 O LEU H 188 -0.074 27.743 20.102 1.00 45.28 B o
ATOM 4589 N THR H 189 0.390 26.466 21.897 1.00 39.28 B N
ATOM 4590 CA THR H 189 0.552 25.235 21.133 1.00 36.51 B c
ATOM 4591 CB THR H 189 1.229 25.498 19.774 1.00 20.00 B c
ATOM 4592 OG1 THR H 189 2.554 26.001 19.986 1.00 20.00 B o
ATOM 4593 CG2 THR H 189 0.430 26.512 18.968 1.00 20.00 B c
ATOM 4594 C THR H 189 1.362 24.208 21.926 1.00 45.83 B c
ATOM 4595 O THR H 189 1.419 24.267 23.154 1.00 42.57 B o
ATOM 4596 N SER H 190 1.947 23.241 21.226 1.00 40.44 B N
ATOM 4597 CA SER H 190 2.691 22.171 21.881 1.00 41.82 B c
ATOM 4598 CB SER H 190 2.022 20.815 21.632 1.00 20.00 B c
ATOM 4599 OG SER H 190 2.225 20.376 20.300 1.00 20.00 B o
ATOM 4600 C SER H 190 4.152 22.141 21.437 1.00 33.81 B c
ATOM 4601 O SER H 190 4.473 22.505 20.306 1.00 49.61 B o ATOM 4602 N LYS H 191 5.040 21.855 22.385 1.00 37.37 B N
ATOM 4603 CA LYS H 191 6.463 21.711 22.098 1.00 41.23 B C
ATOM 4604 CB LYS H 191 7.285 22.617 23.021 1.00 20.00 B C
ATOM 4605 CG LYS H 191 7.104 24.102 22.750 1.00 20.00 B c
ATOM 4606 CD LYS H 191 7.981 24.949 23.658 1.00 20.00 B c
ATOM 4607 CE LYS H 191 7.790 26.435 23.369 1.00 20.00 B c
ATOM 4608 NZ LYS H 191 8.364 27.306 24.434 1.00 20.00 B N
ATOM 4609 C LYS H 191 6.906 20.260 22.268 1.00 35.03 B c
ATOM 4610 O LYS H 191 6.828 19.710 23.365 1.00 40.06 B o
ATOM 4611 N VAL H 192 7.443 19.670 21.205 1.00 33.70 B N
ATOM 4612 CA VAL H 192 7.787 18.250 21.221 1.00 27.61 B c
ATOM 4613 CB VAL H 192 6.974 17.456 20.182 1.00 20.00 B c
ATOM 4614 CGI VAL H 192 7.313 15.975 20.263 1.00 20.00 B c
ATOM 4615 CG2 VAL H 192 5.487 17.679 20.391 1.00 20.00 B c
ATOM 4616 C VAL H 192 9.277 18.011 20.985 1.00 31.74 B c
ATOM 4617 O VAL H 192 9.931 18.771 20.272 1.00 25.58 B o
ATOM 4618 N LEU H 193 9.792 16.921 21.550 1.00 28.88 B N
ATOM 4619 CA LEU H 193 11.190 16.530 21.360 1.00 34.36 B c
ATOM 4620 CB LEU H 193 12.061 17.069 22.505 1.00 20.00 B c
ATOM 4621 CG LEU H 193 12.332 18.577 22.614 1.00 20.00 B c
ATOM 4622 CD1 LEU H 193 12.987 18.914 23.949 1.00 20.00 B c
ATOM 4623 CD2 LEU H 193 13.194 19.076 21.459 1.00 20.00 B c
ATOM 4624 C LEU H 193 11.335 15.008 21.281 1.00 33.03 B c
ATOM 4625 O LEU H 193 11.373 14.331 22.310 1.00 44.93 B o
ATOM 4626 N ASP H 194 11.579 14.498 20.077 1.00 35.09 B N
ATOM 4627 CA ASP H 194 11.209 13.127 19.730 1.00 41.39 B c
ATOM 4628 CB ASP H 194 11.269 12.925 18.214 1.00 20.00 B c
ATOM 4629 CG ASP H 194 10.132 13.626 17.485 1.00 20.00 B c
ATOM 4630 OD1 ASP H 194 9.081 13.873 18.115 1.00 20.00 B o
ATOM 4631 OD2 ASP H 194 10.305 13.969 16.296 1.00 20.00 B o
ATOM 4632 C ASP H 194 12.091 12.100 20.433 1.00 38.04 B c
ATOM 4633 O ASP H 194 11.796 10.904 20.429 1.00 48.03 B o
ATOM 4634 N LEU H 195 13.174 12.576 21.039 1.00 43.64 B N
ATOM 4635 CA LEU H 195 14.206 11.690 21.555 1.00 35.97 B c
ATOM 4636 CB LEU H 195 15.532 11.935 20.832 1.00 20.00 B c
ATOM 4637 CG LEU H 195 15.563 11.586 19.340 1.00 20.00 B c
ATOM 4638 CD1 LEU H 195 16.947 11.852 18.750 1.00 20.00 B c
ATOM 4639 CD2 LEU H 195 15.118 10.144 19.081 1.00 20.00 B c
ATOM 4640 C LEU H 195 14.386 11.839 23.063 1.00 43.63 B c
ATOM 4641 O LEU H 195 15.068 11.036 23.699 1.00 34.71 B o
ATOM 4642 N ASN H 196 13.689 12.808 23.645 1.00 44.30 B N
ATOM 4643 CA ASN H 196 13.886 13.151 25.047 1.00 42.38 B c
ATOM 4644 CB ASN H 196 12.955 14.290 25.454 1.00 20.00 B c
ATOM 4645 CG ASN H 196 13.376 15.618 24.868 1.00 20.00 B c
ATOM 4646 OD1 ASN H 196 14.538 15.815 24.513 1.00 20.00 B o
ATOM 4647 ND2 ASN H 196 12.439 16.555 24.800 1.00 20.00 B N
ATOM 4648 C ASN H 196 13.721 11.972 26.000 1.00 43.66 B c
ATOM 4649 O ASN H 196 14.499 11.814 26.940 1.00 33.62 B o
ATOM 4650 N ASN H 197 12.649 11.208 25.817 1.00 34.31 B N
ATOM 4651 CA ASN H 197 12.370 10.074 26.691 1.00 38.83 B c
ATOM 4652 CB ASN H 197 11.043 9.417 26.318 1.00 20.00 B c
ATOM 4653 CG ASN H 197 9.848 10.251 26.729 1.00 20.00 B c
ATOM 4654 OD1 ASN H 197 9.957 11.129 27.585 1.00 20.00 B o
ATOM 4655 ND2 ASN H 197 8.722 10.042 26.059 1.00 20.00 B N
ATOM 4656 C ASN H 197 13.492 9.042 26.685 1.00 39.90 B c
ATOM 4657 O ASN H 197 14.026 8.687 27.735 1.00 39.04 B o
ATOM 4658 N TY H 198 13.871 8.590 25.495 1.00 35.09 B N
ATOM 4659 CA TYPv H 198 14.992 7.672 25.355 1.00 41.03 B c
ATOM 4660 CB TYP H 198 15.246 7.355 23.882 1.00 20.00 B c
ATOM 4661 CG TYPv H 198 14.109 6.617 23.218 1.00 20.00 B c ATOM 4662 CD1 TY H 198 14.014 5.235 23.294 1.00 20.00 B C
ATOM 4663 CE1 TYR H 198 12.963 4.558 22.712 1.00 20.00 B C
ATOM 4664 CZ TY H 198 11.999 5.265 22.024 1.00 20.00 B c
ATOM 4665 OH TYR H 198 10.967 4.598 21.403 1.00 20.00 B o
ATOM 4666 CE2 TYR H 198 12.073 6.638 21.934 1.00 20.00 B c
ATOM 4667 CD2 TYR H 198 13.120 7.305 22.533 1.00 20.00 B c
ATOM 4668 C TYR H 198 16.252 8.234 26.002 1.00 43.65 B c
ATOM 4669 O TYR H 198 16.940 7.533 26.744 1.00 52.37 B o
ATOM 4670 N ILE H 199 16.464 9.537 25.831 1.00 35.86 B N
ATOM 4671 CA ILE H 199 17.634 10.219 26.386 1.00 45.39 B c
ATOM 4672 CB ILE H 199 17.722 11.682 25.904 1.00 20.00 B c
ATOM 4673 CGI ILE H 199 18.102 11.741 24.425 1.00 20.00 B c
ATOM 4674 CD1 ILE H 199 18.674 13.078 24.004 1.00 20.00 B c
ATOM 4675 CG2 ILE H 199 18.730 12.457 26.735 1.00 20.00 B c
ATOM 4676 C ILE H 199 17.639 10.200 27.912 1.00 37.89 B c
ATOM 4677 O ILE H 199 18.667 9.941 28.538 1.00 45.28 B O
ATOM 4678 N ASP H 200 16.492 10.508 28.505 1.00 37.36 B N
ATOM 4679 CA ASP H 200 16.368 10.551 29.954 1.00 46.66 B c
ATOM 4680 CB ASP H 200 14.992 11.080 30.354 1.00 20.00 B c
ATOM 4681 CG ASP H 200 14.837 12.564 30.083 1.00 20.00 B c
ATOM 4682 OD1 ASP H 200 15.826 13.308 30.264 1.00 20.00 B o
ATOM 4683 OD2 ASP H 200 13.718 12.992 29.721 1.00 20.00 B o
ATOM 4684 C ASP H 200 16.600 9.181 30.581 1.00 51.05 B c
ATOM 4685 O ASP H 200 16.986 9.081 31.745 1.00 57.39 B o
ATOM 4686 N LYS H 201 16.346 8.129 29.810 1.00 57.68 B N
ATOM 4687 CA LYS H 201 16.517 6.766 30.299 1.00 44.02 B c
ATOM 4688 CB LYS H 201 15.747 5.778 29.423 1.00 20.00 B c
ATOM 4689 CG LYS H 201 14.242 5.854 29.602 1.00 20.00 B c
ATOM 4690 CD LYS H 201 13.531 4.795 28.781 1.00 20.00 B c
ATOM 4691 CE LYS H 201 12.030 5.042 28.737 1.00 20.00 B c
ATOM 4692 NZ LYS H 201 11.346 4.192 27.722 1.00 20.00 B N
ATOM 4693 C LYS H 201 17.985 6.366 30.373 1.00 43.56 B c
ATOM 4694 O LYS H 201 18.348 5.447 31.105 1.00 51.34 B o
ATOM 4695 N GLN H 202 18.832 7.074 29.633 1.00 46.06 B N
ATOM 4696 CA GLN H 202 20.216 6.648 29.445 1.00 44.95 B c
ATOM 4697 CB GLN H 202 20.507 6.398 27.963 1.00 20.00 B c
ATOM 4698 CG GLN H 202 19.685 5.270 27.351 1.00 20.00 B c
ATOM 4699 CD GLN H 202 19.894 5.134 25.853 1.00 20.00 B c
ATOM 4700 OE1 GLN H 202 20.323 6.075 25.184 1.00 20.00 B o
ATOM 4701 NE2 GLN H 202 19.513 3.984 25.309 1.00 20.00 B N
ATOM 4702 C GLN H 202 21.245 7.616 30.044 1.00 42.35 B c
ATOM 4703 O GLN H 202 22.376 7.224 30.335 1.00 47.00 B o
ATOM 4704 N LEU H 203 20.852 8.874 30.228 1.00 49.55 B N
ATOM 4705 CA LEU H 203 21.762 9.902 30.735 1.00 50.77 B c
ATOM 4706 CB LEU H 203 21.119 11.283 30.618 1.00 20.00 B c
ATOM 4707 CG LEU H 203 20.836 11.775 29.202 1.00 20.00 B c
ATOM 4708 CD1 LEU H 203 20.093 13.100 29.256 1.00 20.00 B c
ATOM 4709 CD2 LEU H 203 22.134 11.910 28.422 1.00 20.00 B c
ATOM 4710 C LEU H 203 22.148 9.656 32.190 1.00 52.51 B c
ATOM 4711 O LEU H 203 21.273 9.564 33.050 1.00 46.02 B o
ATOM 4712 N LEU H 204 23.439 9.786 32.490 1.00 51.45 B N
ATOM 4713 CA LEU H 204 23.928 9.661 33.865 1.00 58.44 B c
ATOM 4714 CB LEU H 204 25.423 9.333 33.885 1.00 20.00 B c
ATOM 4715 CG LEU H 204 25.848 7.919 33.484 1.00 20.00 B c
ATOM 4716 CD1 LEU H 204 27.346 7.764 33.658 1.00 20.00 B c
ATOM 4717 CD2 LEU H 204 25.112 6.874 34.306 1.00 20.00 B c
ATOM 4718 C LEU H 204 23.661 10.930 34.667 1.00 54.99 B c
ATOM 4719 O LEU H 204 23.740 12.035 34.131 1.00 55.13 B o
ATOM 4720 N PRO H 205 23.414 10.775 35.977 1.00 58.64 B N
ATOM 4721 CA PRO H 205 22.981 11.935 36.734 1.00 52.19 B c ATOM 4722 CB PRO H 205 22.776 11.363 38.137 1.00 20.00 B C
ATOM 4723 CG PRO H 205 23.735 10.190 38.219 1.00 20.00 B C
ATOM 4724 CD PRO H 205 24.191 9.850 36.818 1.00 20.00 B c
ATOM 4725 C PRO H 205 24.112 12.948 36.754 1.00 54.30 B c
ATOM 4726 O PRO H 205 23.898 14.128 37.030 1.00 70.22 B o
ATOM 4727 N ILE H 206 25.316 12.460 36.481 1.00 62.70 B N
ATOM 4728 CA ILE H 206 26.487 13.308 36.354 1.00 68.19 B c
ATOM 4729 CB ILE H 206 27.225 13.445 37.696 1.00 20.00 B c
ATOM 4730 CGI ILE H 206 26.350 14.186 38.709 1.00 20.00 B c
ATOM 4731 CD1 ILE H 206 26.843 14.078 40.136 1.00 20.00 B c
ATOM 4732 CG2 ILE H 206 28.553 14.161 37.505 1.00 20.00 B c
ATOM 4733 C ILE H 206 27.439 12.723 35.321 1.00 62.35 B c
ATOM 4734 O ILE H 206 27.594 11.505 35.221 1.00 67.16 B o
ATOM 4735 N VAL H 207 28.023 13.596 34.510 1.00 52.22 B N
ATOM 4736 CA VAL H 207 28.952 13.168 33.480 1.00 51.31 B c
ATOM 4737 CB VAL H 207 28.568 13.742 32.111 1.00 20.00 B c
ATOM 4738 CGI VAL H 207 29.545 13.261 31.047 1.00 20.00 B C
ATOM 4739 CG2 VAL H 207 27.136 13.356 31.758 1.00 20.00 B C
ATOM 4740 C VAL H 207 30.378 13.582 33.821 1.00 62.09 B c
ATOM 4741 O VAL H 207 30.751 14.746 33.673 1.00 58.88 B o
ATOM 4742 N ASN H 208 31.140 12.641 34.367 1.00 71.72 B N
ATOM 4743 CA ASN H 208 32.533 12.886 34.707 1.00 70.92 B c
ATOM 4744 CB ASN H 208 32.855 12.307 36.086 1.00 20.00 B c
ATOM 4745 CG ASN H 208 32.187 13.074 37.209 1.00 20.00 B c
ATOM 4746 OD1 ASN H 208 31.862 14.252 37.065 1.00 20.00 B O
ATOM 4747 ND2 ASN H 208 31.993 12.411 38.344 1.00 20.00 B N
ATOM 4748 C ASN H 208 33.484 12.312 33.665 1.00 63.05 B c
ATOM 4749 O ASN H 208 33.051 11.778 32.645 1.00 61.34 B o
ATOM 4750 N LYS H 209 34.776 12.337 33.979 1.00 68.91 B N
ATOM 4751 CA LYS H 209 35.811 11.927 33.037 1.00 59.11 B c
ATOM 4752 CB LYS H 209 37.190 12.378 33.528 1.00 20.00 B c
ATOM 4753 CG LYS H 209 37.362 13.888 33.639 1.00 20.00 B c
ATOM 4754 CD LYS H 209 38.689 14.243 34.302 1.00 20.00 B c
ATOM 4755 CE LYS H 209 38.914 15.748 34.344 1.00 20.00 B c
ATOM 4756 NZ LYS H 209 40.286 16.091 34.815 1.00 20.00 B N
ATOM 4757 C LYS H 209 35.810 10.415 32.817 1.00 50.69 B c
ATOM 4758 O LYS H 209 36.500 9.910 31.932 1.00 51.01 B o
ATOM 4759 N GLN H 210 35.116 9.691 33.689 1.00 44.68 B N
ATOM 4760 CA GLN H 210 34.957 8.249 33.528 1.00 49.52 B c
ATOM 4761 CB GLN H 210 34.767 7.581 34.890 1.00 20.00 B c
ATOM 4762 CG GLN H 210 35.976 7.671 35.803 1.00 20.00 B c
ATOM 4763 CD GLN H 210 35.727 7.036 37.156 1.00 20.00 B c
ATOM 4764 OE1 GLN H 210 34.591 6.983 37.629 1.00 20.00 B o
ATOM 4765 NE2 GLN H 210 36.792 6.571 37.798 1.00 20.00 B N
ATOM 4766 C GLN H 210 33.765 7.937 32.632 1.00 62.08 B c
ATOM 4767 O GLN H 210 33.906 7.310 31.580 1.00 80.43 B o
ATOM 4768 N SER H 211 32.599 8.424 33.040 1.00 58.92 B N
ATOM 4769 CA SER H 211 31.384 8.297 32.251 1.00 47.88 B c
ATOM 4770 CB SER H 211 30.270 9.156 32.857 1.00 20.00 B c
ATOM 4771 OG SER H 211 30.733 10.462 33.169 1.00 20.00 B o
ATOM 4772 C SER H 211 31.609 8.665 30.783 1.00 57.32 B c
ATOM 4773 O SER H 211 31.138 7.967 29.884 1.00 50.74 B o
ATOM 4774 N CYS H 212 32.412 9.699 30.545 1.00 44.34 B N
ATOM 4775 CA CYS H 212 32.520 10.292 29.213 1.00 57.52 B c
ATOM 4776 CB CYS H 212 33.762 11.204 29.075 1.00 20.00 B c
ATOM 4777 SG CYS H 212 33.808 12.659 30.229 1.00 20.00 B s
ATOM 4778 C CYS H 212 32.395 9.264 28.073 1.00 60.91 B c
ATOM 4779 O CYS H 212 31.468 9.353 27.272 1.00 52.17 B o
ATOM 4780 N SER H 213 33.381 8.374 27.965 1.00 21.55 B N
ATOM 4781 CA SER H 213 33.462 7.484 26.814 1.00 21.67 B c ATOM 4782 CB SE H 213 34.765 6.678 26.855 1.00 21.81 B C
ATOM 4783 OG SER H 213 35.892 7.530 26.960 1.00 23.00 B O
ATOM 4784 C SER H 213 32.284 6.537 26.686 1.00 21.45 B C
ATOM 4785 O SER H 213 31.711 6.410 25.603 1.00 21.98 B O
ATOM 4786 N ILE H 214 31.895 5.885 27.776 1.00 20.90 B N
ATOM 4787 CA ILE H 214 30.691 5.081 27.699 1.00 20.45 B C
ATOM 4788 CB ILE H 214 30.475 4.234 28.960 1.00 20.53 B C
ATOM 4789 CGI ILE H 214 31.411 3.025 28.946 1.00 20.46 B C
ATOM 4790 CD1 ILE H 214 31.049 1.951 29.952 1.00 21.75 B C
ATOM 4791 CG2 ILE H 214 29.021 3.787 29.052 1.00 20.34 B C
ATOM 4792 C ILE H 214 29.526 6.035 27.523 1.00 20.15 B C
ATOM 4793 O ILE H 214 28.694 5.870 26.631 1.00 19.91 B O
ATOM 4794 N SER H 215 29.528 7.080 28.346 1.00 19.84 B N
ATOM 4795 CA SER H 215 28.475 8.080 28.330 1.00 19.58 B C
ATOM 4796 CB SER H 215 28.663 9.070 29.478 1.00 19.76 B C
ATOM 4797 OG SER H 215 27.637 10.048 29.470 1.00 19.97 B O
ATOM 4798 C SER H 215 28.460 8.825 27.017 1.00 19.34 B C
ATOM 4799 O SER H 215 27.406 9.053 26.446 1.00 19.54 B O
ATOM 4800 N ASN H 216 29.638 9.187 26.527 1.00 18.80 B N
ATOM 4801 CA ASN H 216 29.724 9.885 25.258 1.00 18.36 B C
ATOM 4802 CB ASN H 216 31.156 10.336 24.972 1.00 18.41 B C
ATOM 4803 CG ASN H 216 31.647 11.377 25.959 1.00 19.55 B C
ATOM 4804 OD1 ASN H 216 31.028 12.428 26.133 1.00 20.52 B O
ATOM 4805 ND2 ASN H 216 32.779 11.100 26.597 1.00 20.43 B N
ATOM 4806 C ASN H 216 29.211 9.010 24.129 1.00 17.78 B C
ATOM 4807 O ASN H 216 28.481 9.479 23.255 1.00 17.91 B O
ATOM 4808 N ILE H 217 29.570 7.730 24.150 1.00 17.02 B N
ATOM 4809 CA ILE H 217 29.110 6.845 23.095 1.00 16.60 B C
ATOM 4810 CB ILE H 217 29.718 5.439 23.210 1.00 16.46 B C
ATOM 4811 CGI ILE H 217 31.093 5.403 22.540 1.00 16.26 B C
ATOM 4812 CD1 ILE H 217 31.610 4.001 22.276 1.00 16.44 B C
ATOM 4813 CG2 ILE H 217 28.791 4.408 22.591 1.00 16.70 B C
ATOM 4814 C ILE H 217 27.599 6.750 23.148 1.00 16.73 B C
ATOM 4815 O ILE H 217 26.923 6.809 22.116 1.00 16.80 B O
ATOM 4816 N GLU H 218 27.064 6.639 24.360 1.00 17.02 B N
ATOM 4817 CA GLU H 218 25.631 6.500 24.526 1.00 17.70 B C
ATOM 4818 CB GLU H 218 25.266 6.321 26.000 1.00 18.20 B C
ATOM 4819 CG GLU H 218 25.955 5.155 26.685 1.00 21.31 B C
ATOM 4820 CD GLU H 218 25.270 4.774 27.986 1.00 25.72 B C
ATOM 4821 OE1 GLU H 218 25.558 5.409 29.023 1.00 26.96 B O
ATOM 4822 OE2 GLU H 218 24.447 3.835 27.975 1.00 27.07 B O
ATOM 4823 C GLU H 218 24.951 7.742 23.995 1.00 17.29 B C
ATOM 4824 O GLU H 218 23.942 7.660 23.312 1.00 17.62 B O
ATOM 4825 N THR H 219 25.482 8.931 24.255 1.00 16.62 B N
ATOM 4826 CA THR H 219 24.786 10.141 23.789 1.00 15.95 B C
ATOM 4827 CB THR H 219 25.475 11.413 24.325 1.00 15.95 B C
ATOM 4828 OG1 THR H 219 25.394 11.438 25.756 1.00 15.63 B O
ATOM 4829 CG2 THR H 219 24.814 12.661 23.759 1.00 15.97 B C
ATOM 4830 C THR H 219 24.646 10.261 22.254 1.00 15.64 B C
ATOM 4831 O THR H 219 23.557 10.569 21.720 1.00 15.93 B O
ATOM 4832 N VAL H 220 25.737 9.974 21.550 1.00 14.98 B N
ATOM 4833 CA VAL H 220 25.773 10.074 20.093 1.00 14.51 B C
ATOM 4834 CB VAL H 220 27.177 9.738 19.559 1.00 14.29 B C
ATOM 4835 CGI VAL H 220 27.191 9.771 18.041 1.00 14.24 B C
ATOM 4836 CG2 VAL H 220 28.213 10.693 20.137 1.00 14.10 B C
ATOM 4837 C VAL H 220 24.779 9.088 19.498 1.00 14.64 B C
ATOM 4838 O VAL H 220 24.030 9.390 18.544 1.00 14.79 B O
ATOM 4839 N ILE H 221 24.762 7.904 20.097 1.00 14.43 B N
ATOM 4840 CA ILE H 221 23.860 6.856 19.674 1.00 14.36 B C
ATOM 4841 CB ILE H 221 24.067 5.569 20.487 1.00 14.03 B C ATOM 4842 CGI ILE H 221 25.394 4.909 20.110 1.00 13.72 B C
ATOM 4843 CD1 ILE H 221 25.493 4.526 18.649 1.00 14.17 B C
ATOM 4844 CG2 ILE H 221 22.908 4.611 20.267 1.00 13.91 B c
ATOM 4845 C ILE H 221 22.443 7.351 19.869 1.00 14.82 B C
ATOM 4846 O ILE H 221 21.589 7.132 19.023 1.00 14.82 B O
ATOM 4847 N GLU H 222 22.195 8.039 20.978 1.00 15.51 B N
ATOM 4848 CA GLU H 222 20.857 8.551 21.246 1.00 16.52 B c
ATOM 4849 CB GLU H 222 20.733 9.113 22.663 1.00 16.80 B c
ATOM 4850 CG GLU H 222 20.725 8.043 23.747 1.00 19.14 B c
ATOM 4851 CD GLU H 222 19.637 8.267 24.780 1.00 22.62 B c
ATOM 4852 OE1 GLU H 222 19.965 8.662 25.919 1.00 24.35 B o
ATOM 4853 OE2 GLU H 222 18.453 8.039 24.454 1.00 23.98 B o
ATOM 4854 C GLU H 222 20.400 9.566 20.199 1.00 16.65 B c
ATOM 4855 O GLU H 222 19.255 9.541 19.792 1.00 16.95 B o
ATOM 4856 N PHE H 223 21.292 10.444 19.752 1.00 16.70 B N
ATOM 4857 CA PHE H 223 20.971 11.413 18.690 1.00 16.95 B c
ATOM 4858 CB PHE H 223 22.259 12.227 18.509 1.00 16.85 B c
ATOM 4859 CG PHE H 223 22.154 13.406 17.593 1.00 17.23 B c
ATOM 4860 CD1 PHE H 223 21.522 14.570 17.995 1.00 17.98 B c
ATOM 4861 CE1 PHE H 223 21.467 15.667 17.155 1.00 18.28 B c
ATOM 4862 CZ PHE H 223 22.071 15.616 15.914 1.00 18.19 B c
ATOM 4863 CE2 PHE H 223 22.726 14.469 15.516 1.00 18.14 B c
ATOM 4864 CD2 PHE H 223 22.776 13.380 16.357 1.00 17.75 B c
ATOM 4865 C PHE H 223 20.601 10.675 17.371 1.00 17.28 B c
ATOM 4866 O PHE H 223 19.564 10.951 16.650 1.00 17.17 B o
ATOM 4867 N GLN H 224 21.422 9.671 17.091 1.00 17.62 B N
ATOM 4868 CA GLN H 224 21.209 8.880 15.894 1.00 18.16 B c
ATOM 4869 CB GLN H 224 22.390 7.930 15.652 1.00 18.51 B c
ATOM 4870 CG GLN H 224 23.751 8.594 15.888 1.00 20.06 B c
ATOM 4871 CD GLN H 224 24.867 8.009 15.039 1.00 22.03 B c
ATOM 4872 OE1 GLN H 224 24.920 6.800 14.806 1.00 22.15 B o
ATOM 4873 NE2 GLN H 224 25.783 8.864 14.595 1.00 22.11 B N
ATOM 4874 C GLN H 224 19.855 8.158 15.956 1.00 18.04 B c
ATOM 4875 O GLN H 224 19.196 7.981 14.932 1.00 18.17 B o
ATOM 4876 N GLN H 225 19.488 7.701 17.156 1.00 17.90 B N
ATOM 4877 CA GLN H 225 18.192 7.079 17.492 1.00 17.95 B c
ATOM 4878 CB GLN H 225 18.271 6.408 18.861 1.00 18.13 B c
ATOM 4879 CG GLN H 225 19.251 5.257 18.893 1.00 19.04 B c
ATOM 4880 CD GLN H 225 18.854 4.196 19.891 1.00 21.22 B c
ATOM 4881 OE1 GLN H 225 17.834 4.321 20.569 1.00 22.55 B o
ATOM 4882 NE2 GLN H 225 19.651 3.142 19.985 1.00 22.48 B N
ATOM 4883 C GLN H 225 16.993 8.032 17.430 1.00 17.84 B c
ATOM 4884 O GLN H 225 15.872 7.657 17.090 1.00 17.71 B o
ATOM 4885 N LYS H 226 18.593 9.729 17.758 1.00 17.95 B N
ATOM 4886 CA LYS H 226 17.704 10.870 17.777 1.00 18.00 B c
ATOM 4887 CB LYS H 226 18.471 12.167 18.045 1.00 18.21 B c
ATOM 4888 CG LYS H 226 19.258 12.240 19.342 1.00 18.50 B c
ATOM 4889 CD LYS H 226 18.743 13.353 20.242 1.00 19.87 B c
ATOM 4890 CE LYS H 226 19.762 13.696 21.316 1.00 21.36 B c
ATOM 4891 NZ LYS H 226 19.374 14.909 22.085 1.00 21.83 B N
ATOM 4892 C LYS H 226 17.251 10.914 16.350 1.00 17.84 B c
ATOM 4893 O LYS H 226 16.195 11.458 16.046 1.00 17.94 B o
ATOM 4894 N ASN H 227 18.025 10.304 15.460 1.00 17.70 B N
ATOM 4895 CA ASN H 227 17.467 10.197 14.086 1.00 17.66 B c
ATOM 4896 CB ASN H 227 18.366 9.273 13.270 1.00 17.36 B c
ATOM 4897 CG ASN H 227 19.700 9.884 12.927 1.00 17.40 B c
ATOM 4898 OD1 ASN H 227 20.438 9.337 12.107 1.00 17.84 B o
ATOM 4899 ND2 ASN H 227 20.025 11.011 13.545 1.00 17.22 B , N
ATOM 4900 C ASN H 227 16.016 9.596 13.857 1.00 17.76 B c
ATOM 4901 O ASN H 227 15.214 10.239 13.175 1.00 17.92 B o ATOM 4902 N ASN H 228 15.655 8.431 14.418 1.00 17.78 B N
ATOM 4903 CA ASN H 228 14.290 7.922 14.435 1.00 17.59 B C
ATOM 4904 CB ASN H 228 14.003 7.185 15.743 1.00 17.89 B C
ATOM 4905 CG ASN H 228 14.845 5.934 15.903 1.00 18.43 B C
ATOM 4906 OD1 ASN H 228 15.432 5.698 16.959 1.00 18.74 B O
ATOM 4907 ND2 ASN H 228 14.908 5.124 14.852 1.00 18.61 B N
ATOM 4908 C ASN H 228 13.335 9.091 14.265 1.00 17.09 B C
ATOM 4909 O ASN H 228 12.380 9.032 13.490 1.00 17.17 B O
ATOM 4910 N A G H 229 13.267 9.880 15.306 1.00 16.33 B N
ATOM 4911 CA ARG H 229 12.252 10.885 15.298 1.00 15.76 B C
ATOM 4912 CB ARG H 229 11.906 11.215 16.758 1.00 15.70 B C
ATOM 4913 CG ARG H 229 11.667 9.916 17.580 1.00 14.99 B C
ATOM 4914 CD ARG H 229 11.240 10.128 19.039 1.00 15.33 B C
ATOM 4915 NE ARG H 229 12.372 10.516 19.868 1.00 15.59 B N
ATOM 4916 CZ ARG H 229 13.209 9.663 20.448 1.00 15.85 B C
ATOM 4917 NH1 ARG H 229 13.045 8.350 20.313 1.00 16.20 B N
ATOM 4918 NH2 ARG H 229 14.216 10.134 21.168 1.00 16.63 B N
ATOM 4919 C ARG H 229 12.960 11.937 14.490 1.00 15.62 B C
ATOM 4920 O ARG H 229 12.436 12.586 13.561 1.00 15.73 B O
ATOM 4921 N LEU H 230 14.249 11.935 14.783 1.00 15.46 B N
ATOM 4922 CA LEU H 230 15.146 12.972 14.402 1.00 15.22 B C
ATOM 4923 CB LEU H 230 16.334 12.863 15.348 1.00 15.08 B C
ATOM 4924 CG LEU H 230 17.100 14.054 15.896 1.00 14.70 B C
ATOM 4925 CD1 LEU H 230 16.465 14.590 17.171 1.00 15.19 B C
ATOM 4926 CD2 LEU H 230 18.500 13.564 16.165 1.00 15.46 B C
ATOM 4927 C LEU H 230 15.658 12.853 12.989 1.00 15.31 B C
ATOM 4928 O LEU H 230 15.224 13.608 12.133 1.00 15.46 B O
ATOM 4929 N LEU H 231 16.533 11.890 12.727 1.00 15.48 B N
ATOM 4930 CA LEU H 231 17.158 11.825 11.423 1.00 15.75 B C
ATOM 4931 CB LEU H 231 18.215 10.722 11.423 1.00 15.90 B C
ATOM 4932 CG LEU H 231 19.366 10.875 12.416 1.00 16.63 B C
ATOM 4933 CD1 LEU H 231 20.443 9.836 12.133 1.00 18.45 B C
ATOM 4934 CD2 LEU H 231 19.953 12.276 12.366 1.00 16.67 B C
ATOM 4935 C LEU H 231 16.139 11.575 10.324 1.00 15.76 B C
ATOM 4936 O LEU H 231 16.121 12.269 9.309 1.00 15.84 B O
ATOM 4937 N GLU H 232 15.249 10.617 10.561 1.00 15.71 B N
ATOM 4938 CA GLU H 232 14.200 10.308 9.607 1.00 15.93 B C
ATOM 4939 CB GLU H 232 13.470 9.012 10.001 1.00 16.15 B C
ATOM 4940 CG GLU H 232 14.389 7.801 10.158 1.00 18.59 B C
ATOM 4941 CD GLU H 232 14.567 6.988 8.876 1.00 21.47 B C
ATOM 4942 OE1 GLU H 232 13.976 7.355 7.839 1.00 22.14 B O
ATOM 4943 OE2 GLU H 232 15.298 5.973 8.907 1.00 23.34 B O
ATOM 4944 C GLU H 232 13.241 11.482 9.456 1.00 15.45 B C
ATOM 4945 O GLU H 232 12.881 11.860 8.328 1.00 15.95 B O
ATOM 4946 N ILE H 233 12.855 12.113 10.564 1.00 14.54 B N
ATOM 4947 CA ILE H 233 11.941 13.221 10.375 1.00 13.69 B C
ATOM 4948 CB ILE H 233 11.444 13.775 11.699 1.00 13.63 B C
ATOM 4949 CGI ILE H 233 10.497 12.763 12.326 1.00 13.58 B C
ATOM 4950 CD1 ILE H 233 9.817 13.280 13.532 1.00 13.55 B C
ATOM 4951 CG2 ILE H 233 10.682 15.070 11.490 1.00 13.88 B C
ATOM 4952 C ILE H 233 12.605 14.309 9.526 1.00 13.28 B C
ATOM 4953 O ILE H 233 11.972 14.914 8.653 1.00 13.04 B O
ATOM 4954 N THR H 234 13.888 14.544 9.773 1.00 13.18 B N
ATOM 4955 CA THR H 234 14.620 15.575 9.063 1.00 13.39 B C
ATOM 4956 CB THR H 234 16.082 15.655 9.574 1.00 13.21 B C
ATOM 4957 OG1 THR H 234 16.099 15.927 10.978 1.00 13.15 B O
ATOM 4958 CG2 THR H 234 16.870 16.740 8.846 1.00 13.22 B C
ATOM 4959 C THR H 234 14.686 15.273 7.577 1.00 13.76 B C
ATOM 4960 O THR H 234 14.434 16.152 6.738 1.00 13.95 B O
ATOM 4961 N ARG H 235 14.994 14.024 7.240 1.00 14.26 B N ATOM 4962 CA ARG H 235 15.119 13.686 5.831 1.00 14.92 B C
ATOM 4963 CB ARG H 235 15.574 12.242 5.661 1.00 15.30 B C
ATOM 4964 CG ARG H 235 14.532 11.325 5.054 1.00 16.27 B C
ATOM 4965 CD ARG H 235 14.829 9.882 5.408 1.00 18.52 B C
ATOM 4966 NE ARG H 235 16.234 9.676 5.746 1.00 17.86 B N
ATOM 4967 CZ ARG H 235 17.190 9.425 4.858 1.00 16.91 B C
ATOM 4968 NHl ARG H 235 16.898 9.354 3.566 1.00 16.59 B N
ATOM 4969 NH2 ARG H 235 18.438 9.249 5.267 1.00 16.86 B N
ATOM 4970 C ARG H 235 13.766 13.887 5.176 1.00 15.05 B C
ATOM 4971 O ARG H 235 13.663 14.432 4.073 1.00 15.15 B O
ATOM 4972 N GLU H 236 12.727 13.474 5.894 1.00 15.18 B N
ATOM 4973 CA GLU H 236 11.375 13.527 5.376 1.00 15.24 B C
ATOM 4974 CB GLU H 236 10.415 12.920 6.403 1.00 15.69 B C
ATOM 4975 CG GLU H 236 9.176 12.265 5.822 1.00 18.22 B C
ATOM 4976 CD GLU H 236 8.355 11.543 6.875 1.00 21.59 B C
ATOM 4977 OE1 GLU H 236 7.200 11.178 6.581 1.00 24.41 B O
ATOM 4978 OE2 GLU H 236 8.857 11.345 8.000 1.00 21.59 B O
ATOM 4979 C GLU H 236 10.987 14.971 5.073 1.00 14.61 B C
ATOM 4980 O GLU H 236 10.396 15.253 4.031 1.00 14.82 B O
ATOM 4981 N PHE H 237 11.333 15.877 5.985 1.00 14.05 B N
ATOM 4982 CA PHE H 237 11.053 17.296 5.809 1.00 13.84 B C
ATOM 4983 CB PHE H 237 11.316 18.065 7.105 1.00 14.04 B C
ATOM 4984 CG PHE H 237 10.142 18.087 8.038 1.00 14.84 B C
ATOM 4985 CD1 PHE H 237 10.224 17.516 9.297 1.00 15.30 B C
ATOM 4986 CE1 PHE H 237 9.142 17.542 10.153 1.00 15.15 B C
ATOM 4987 CZ PHE H 237 7.961 18.135 9.755 1.00 15.19 B C
ATOM 4988 CE2 PHE H 237 7.864 18.704 8.502 1.00 15.02 B C
ATOM 4989 CD2 PHE H 237 8.949 18.677 7.651 1.00 15.03 B C
ATOM 4990 C PHE H 237 11.830 17.909 4.654 1.00 13.51 B C
ATOM 4991 O PHE H 237 11.293 18.687 3.866 1.00 13.43 B O
ATOM 4992 N SER H 238 13.100 17.534 4.554 1.00 13.11 B N
ATOM 4993 CA SER H 238 13.972 18.065 3.516 1.00 12.82 B C
ATOM 4994 CB SER H 238 15.404 17.546 3.691 1.00 12.86 B C
ATOM 4995 OG SER H 238 15.976 17.981 4.916 1.00 12.76 B O
ATOM 4996 C SER H 238 13.411 17.654 2.164 1.00 12.69 B C
ATOM 4997 O SER H 238 13.437 18.425 1.202 1.00 12.63 B O
ATOM 4998 N VAL H 239 12.910 16.426 2.107 1.00 12.59 B N
ATOM 4999 CA VAL H 239 12.361 15.865 0.883 1.00 12.80 B C
ATOM 5000 CB VAL H 239 12.065 14.358 1.041 1.00 12.71 B C
ATOM 5001 CGI VAL H 239 11.359 13.819 -0.193 1.00 13.63 B C
ATOM 5002 CG2 VAL H 239 13.349 13.588 1.316 1.00 13.57 B C
ATOM 5003 C VAL H 239 11.094 16.596 0.443 1.00 12.94 B C
ATOM 5004 O VAL H 239 10.722 16.546 -0.728 1.00 13.10 B O
ATOM 5005 N ASN H 240 10.430 17.274 1.372 1.00 4.15 B N
ATOM 5006 CA ASN H 240 9.074 17.741 1.109 1.00 4.33 B C
ATOM 5007 CB ASN H 240 8.110 17.268 2.199 1.00 4.59 B C
ATOM 5008 CG ASN H 240 7.810 15.784 2.106 1.00 5.36 B C
ATOM 5009 OD1 ASN H 240 7.128 15.331 1.188 1.00 6.27 B O
ATOM 5010 ND2 ASN H 240 8.343 15.016 3.047 1.00 7.15 B N
ATOM 5011 C ASN H 240 8.924 19.242 0.853 1.00 4.19 B C
ATOM 5012 O ASN H 240 7.843 19.707 0.490 1.00 4.19 B O
ATOM 5013 N ALA H 241 10.014 19.990 0.995 1.00 3.93 B N
ATOM 5014 CA ALA H 241 9.948 21.447 0.930 1.00 3.90 B C
ATOM 5015 CB ALA H 241 9.784 21.908 -0.511 1.00 3.86 B C
ATOM 5016 C ALA H 241 8.812 21.985 1.798 1.00 4.22 B C
ATOM 5017 O ALA H 241 7.932 22.697 1.314 1.00 4.47 B O
ATOM 5018 N GLY H 242 8.772 21.540 3.049 1.00 4.53 B N
ATOM 5019 CA GLY H 242 8.055 22.258 4.097 1.00 4.65 B C
ATOM 5020 C GLY H 242 6.563 21.980 4.122 1.00 4.67 B C
ATOM 5021 O GLY H 242 5.792 22.759 4.683 1.00 5.27 B O ATOM 5022 N VAL H 243 6.159 20.841 3.570 1.00 4.37 B N
ATOM 5023 CA VAL H 243 4.755 20.449 3.577 1.00 4.32 B C
ATOM 5024 CB VAL H 243 3.961 21.182 2.477 1.00 3.99 B C
ATOM 5025 CGI VAL H 243 2.519 21.398 2.915 1.00 4.22 B c
ATOM 5026 CG2 VAL H 243 4.629 22.508 2.131 1.00 3.85 B c
ATOM 5027 C VAL H 243 4.595 18.943 3.393 1.00 4.61 B c
ATOM 5028 O VAL H 243 5.201 18.350 2.501 1.00 4.89 B o
ATOM 5029 N TH H 244 3.764 18.333 4.231 1.00 4.95 B N
ATOM 5030 CA TH H 244 3.600 16.886 4.220 1.00 5.71 B c
ATOM 5031 CB TH H 244 4.318 16.226 5.410 1.00 6.11 B c
ATOM 5032 OG1 THR H 244 5.051 17.217 6.140 1.00 7.17 B o
ATOM 5033 CG2 THR H 244 5.273 15.147 4.925 1.00 7.55 B c
ATOM 5034 C THR H 244 2.129 16.505 4.268 1.00 5.61 B c
ATOM 5035 O THR H 244 1.359 17.073 5.042 1.00 5.85 B o
ATOM 5036 N THR H 245 1.786 15.428 3.575 1.00 5.53 B N
ATOM 5037 CA THR H 245 0.617 14.647 3.939 1.00 5.81 B c
ATOM 5038 CB THR H 245 -0.404 14.592 2.788 1.00 6.13 B c
ATOM 5039 OG1 THR H 245 -0.888 15.915 2.517 1.00 8.11 B o
ATOM 5040 CG2 THR H 245 -1.577 13.695 3.154 1.00 6.63 B c
ATOM 5041 C THR H 245 1.032 13.245 4.370 1.00 5.73 B c
ATOM 5042 O THR H 245 2.189 12.861 4.202 1.00 5.86 B o
ATOM 5043 N PRO H 246 0.060 12.433 4.804 1.00 5.68 B N
ATOM 5044 CA PRO H 246 0.078 11.993 6.186 1.00 5.11 B c
ATOM 5045 CB PRO H 246 0.753 10.626 6.084 1.00 5.19 B c
ATOM 5046 CG PRO H 246 0.360 10.124 4.675 1.00 5.90 B c
ATOM 5047 CD PRO H 246 -0.256 11.297 3.926 1.00 6.36 B c
ATOM 5048 C PRO H 246 0.830 12.916 7.140 1.00 4.85 B c
ATOM 5049 O PRO H 246 1.927 13.379 6.825 1.00 5.25 B o
ATOM 5050 N VAL H 247 0.144 13.323 8.205 1.00 4.35 B N
ATOM 5051 CA VAL H 247 0.792 13.950 9.347 1.00 3.82 B c
ATOM 5052 CB VAL H 247 -0.198 14.817 10.157 1.00 3.52 B c
ATOM 5053 CGI VAL H 247 0.558 15.754 11.087 1.00 3.62 B c
ATOM 5054 CG2 VAL H 247 -1.091 15.615 9.217 1.00 3.60 B c
ATOM 5055 C VAL H 247 1.447 12.899 10.242 1.00 3.69 B c
ATOM 5056 O VAL H 247 0.761 12.124 10.913 1.00 3.36 B o
ATOM 5057 N SER H 248 2.748 12.721 10.040 1.00 3.72 B N
ATOM 5058 CA SER H 248 3.496 11.654 10.686 1.00 3.96 B c
ATOM 5059 CB SER H 248 4.995 11.840 10.451 1.00 4.07 B c
ATOM 5060 OG SER H 248 5.525 12.834 11.310 1.00 4.13 B o
ATOM 5061 C SER H 248 3.211 11.615 12.180 1.00 4.35 B c
ATOM 5062 O SER H 248 2.890 12.635 12.788 1.00 4.36 B o
ATOM 5063 N THR H 249 3.458 10.460 12.784 1.00 4.53 B N
ATOM 5064 CA THR H 249 3.489 10.350 14.231 1.00 4.61 B c
ATOM 5065 CB THR H 249 3.682 8.893 14.677 1.00 4.70 B c
ATOM 5066 OG1 THR H 249 5.018 8.473 14.374 1.00 5.42 B o
ATOM 5067 CG2 THR H 249 2.695 7.984 13.961 1.00 4.88 B c
ATOM 5068 C THR H 249 4.589 11.215 14.839 1.00 4.47 B c
ATOM 5069 O THR H 249 4.570 11.491 16.039 1.00 4.74 B o
ATOM 5070 N TYR H 250 5.518 11.684 14.009 1.00 4.32 B N
ATOM 5071 CA TYR H 250 6.544 12.619 14.475 1.00 4.42 B c
ATOM 5072 CB TYR H 250 7.811 12.531 13.625 1.00 4.91 B c
ATOM 5073 CG TYR H 250 8.409 11.148 13.525 1.00 6.81 B c
ATOM 5074 CD1 TYR H 250 8.844 10.657 12.302 1.00 8.89 B c
ATOM 5075 CE1 TYR H 250 9.480 9.437 12.205 1.00 10.73 B c
ATOM 5076 CZ TYR H 250 9.685 8.685 13.341 1.00 12.28 B c
ATOM 5077 OH TYR H 250 10.305 7.460 13.251 1.00 12.24 B o
ATOM 5078 CE2 TYR H 250 9.284 9.161 14.571 1.00 12.15 B c
ATOM 5079 CD2 TYR H 250 8.689 10.405 14.662 1.00 9.81 B c
ATOM 5080 C TYR H 250 6.053 14.064 14.516 1.00 4.21 B c
ATOM 5081 O TYR H 250 6.596 14.883 15.259 1.00 4.20 B o ATOM 5082 N MET H 251 5.148 14.413 13.605 1.00 4.14 B N
ATOM 5083 CA MET H 251 4.517 15.732 13.632 1.00 4.15 B C
ATOM 5084 CB MET H 251 3.798 16.014 12.313 1.00 4.14 B C
ATOM 5085 CG MET H 251 4.720 16.097 11.115 1.00 4.51 B c
ATOM 5086 SD MET H 251 5.733 17.587 11.115 1.00 3.81 B s
ATOM 5087 CE MET H 251 5.601 18.077 9.395 1.00 4.55 B c
ATOM 5088 C MET H 251 3.519 15.806 14.775 1.00 4.13 B c
ATOM 5089 O MET H 251 3.510 16.759 15.555 1.00 4.24 B o
ATOM 5090 N LEU H 252 2.692 14.773 14.874 1.00 4.23 B N
ATOM 5091 CA LEU H 252 1.708 14.681 15.934 1.00 4.22 B c
ATOM 5092 CB LEU H 252 0.302 14.881 15.369 1.00 4.14 B c
ATOM 5093 CG LEU H 252 -0.295 16.282 15.515 1.00 4.05 B c
ATOM 5094 CD1 LEU H 252 -1.813 16.216 15.561 1.00 5.22 B c
ATOM 5095 CD2 LEU H 252 0.245 16.972 16.756 1.00 6.20 B c
ATOM 5096 C LEU H 252 1.818 13.314 16.589 1.00 4.62 B c
ATOM 5097 O LEU H 252 1.906 12.295 15.903 1.00 4.97 B o
ATOM 5098 N TH H 253 1.986 13.314 17.906 1.00 4.90 B N
ATOM 5099 CA THR H 253 1.718 12.126 18.704 1.00 5.57 B c
ATOM 5100 CB THR H 253 2.147 12.323 20.168 1.00 5.55 B c
ATOM 5101 OG1 THR H 253 3.369 13.068 20.214 1.00 6.43 B o
ATOM 5102 CG2 THR H 253 2.362 10.978 20.842 1.00 6.28 B c
ATOM 5103 C THR H 253 0.235 11.775 18.673 1.00 6.03 B c
ATOM 5104 O THR H 253 -0.621 12.663 18.679 1.00 6.68 B o
ATOM 5105 N ASN H 254 -0.066 10.483 18.746 1.00 6.39 B N
ATOM 5106 CA ASN H 254 -1.396 10.040 19.141 1.00 6.79 B c
ATOM 5107 CB ASN H 254 -1.375 8.564 19.534 1.00 6.85 B c
ATOM 5108 CG ASN H 254 -2.758 7.954 19.571 1.00 6.81 B c
ATOM 5109 OD1 ASN H 254 -3.395 7.771 18.534 1.00 7.67 B o
ATOM 5110 ND2 ASN H 254 -3.252 7.682 20.773 1.00 6.19 B N
ATOM 5111 C ASN H 254 -1.956 10.882 20.284 1.00 7.08 B c
ATOM 5112 O ASN H 254 -2.968 11.565 20.125 1.00 6.90 B o
ATOM 5113 N SER H 255 -1.282 10.843 21.430 1.00 7.21 B N
ATOM 5114 CA SER H 255 -1.689 11.633 22.588 1.00 7.37 B c
ATOM 5115 CB SER H 255 -0.561 11.714 23.619 1.00 8.09 B c
ATOM 5116 OG SER H 255 0.228 10.539 23.617 1.00 10.47 B o
ATOM 5117 C SER H 255 -2.102 13.036 22.163 1.00 6.82 B c
ATOM 5118 O SER H 255 -3.192 13.499 22.496 1.00 6.99 B o
ATOM 5119 N GLU H 256 -1.229 13.704 21.415 1.00 6.17 B N
ATOM 5120 CA GLU H 256 -1.485 15.072 20.981 1.00 6.13 B c
ATOM 5121 CB GLU H 256 -0.274 15.644 20.243 1.00 6.22 B c
ATOM 5122 CG GLU H 256 0.847 16.110 21.152 1.00 8.41 B c
ATOM 5123 CD GLU H 256 2.209 15.761 20.596 1.00 10.26 B c
ATOM 5124 OE1 GLU H 256 2.292 15.472 19.384 1.00 11.90 B , o
ATOM 5125 OE2 GLU H 256 3.162 15.626 21.392 1.00 9.55 B o
ATOM 5126 C GLU H 256 -2.706 15.126 20.079 1.00 5.76 B c
ATOM 5127 O GLU H 256 -3.684 15.810 20.380 1.00 5.93 B o
ATOM 5128 N LEU H 257 -2.633 14.420 18.956 1.00 5.67 B N
ATOM 5129 CA LEU H 257 -3.729 14.411 18.002 1.00 5.37 B c
ATOM 5130 CB LEU H 257 -3.543 13.299 16.970 1.00 5.03 B c
ATOM 5131 CG LEU H 257 -4.781 13.003 16.121 1.00 3.65 B c
ATOM 5132 CD1 LEU H 257 -5.114 14.184 15.222 1.00 2.00 B c
ATOM 5133 CD2 LEU H 257 -4.592 11.737 15.305 1.00 2.14 B c
ATOM 5134 C LEU H 257 -5.050 14.223 18.732 1.00 5.64 B c
ATOM 5135 O LEU H 257 -6.020 14.934 18.475 1.00 5.81 B o
ATOM 5136 N LEU H 258 -5.061 13.300 19.687 1.00 5.75 B N
ATOM 5137 CA LEU H 258 -6.297 12.905 20.344 1.00 5.91 B c
ATOM 5138 CB LEU H 258 -6.063 11.693 21.242 1.00 6.10 B c
ATOM 5139 CG LEU H 258 -6.438 10.358 20.605 1.00 5.75 B c
ATOM 5140 CD1 LEU H 258 -5.970 9.206 21.477 1.00 6.33 B c
ATOM 5141 CD2 LEU H 258 -7.939 10.287 20.372 1.00 7.33 B c ATOM 5142 C LEU H 258 -6.908 14.049 21.142 1.00 6.03 B C
ATOM 5143 O LEU H 258 -8.113 14.290 21.071 1.00 5.73 B o
ATOM 5144 N SE H 259 -6.076 14.745 21.910 1.00 6.47 B N
ATOM 5145 CA SE H 259 -6.537 15.883 22.695 1.00 6.95 B C
ATOM 5146 CB SE H 259 -5.521 16.237 23.784 1.00 7.05 B c
ATOM 5147 OG SE H 259 -4.695 17.317 23.383 1.00 6.86 B o
ATOM 5148 C SER H 259 -6.782 17.086 21.795 1.00 6.74 B c
ATOM 5149 O SER H 259 -7.592 17.959 22.110 1.00 6.86 B o
ATOM 5150 N LEU H 260 -6.074 17.125 20.670 1.00 6.31 B N
ATOM 5151 CA LEU H 260 -6.295 18.149 19.657 1.00 6.09 B c
ATOM 5152 CB LEU H 260 -5.239 18.052 18.552 1.00 6.09 B c
ATOM 5153 CG LEU H 260 -4.235 19.203 18.446 1.00 6.24 B c
ATOM 5154 CD1 LEU H 260 -3.350 19.030 17.222 1.00 6.53 B c
ATOM 5155 CD2 LEU H 260 -4.944 20.549 18.407 1.00 5.98 B c
ATOM 5156 C LEU H 260 -7.692 18.026 19.056 1.00 6.25 B c
ATOM 5157 O LEU H 260 -8.428 19.010 18.963 1.00 6.37 B o
ATOM 5158 N ILE H 261 -8.024 16.825 18.596 1.00 6.63 B N
ATOM 5159 CA ILE H 261 -9.395 16.490 18.245 1.00 7.19 B c
ATOM 5160 CB ILE H 261 -9.568 14.975 18.078 1.00 7.09 B c
ATOM 5161 CGI ILE H 261 -9.037 14.528 16.715 1.00 7.46 B c
ATOM 5162 CD1 ILE H 261 -8.132 13.315 16.782 1.00 8.38 B c
ATOM 5163 CG2 ILE H 261 -11.024 14.579 18.262 1.00 6.61 B c
ATOM 5164 C ILE H 261 -10.352 16.980 19.322 1.00 8.01 B i c
ATOM 5165 O ILE H 261 -11.255 17.770 19.051 1.00 8.26 B o
ATOM 5166 N ASN H 262 -10.081 16.586 20.560 1.00 9.05 B N
ATOM 5167 CA ASN H 262 -10.896 17.006 21.689 1.00 9.88 B c
ATOM 5168 CB ASN H 262 -10.175 16.714 23.001 1.00 9.99 B c
ATOM 5169 CG ASN H 262 -11.127 16.353 24.111 1.00 11.16 B c
ATOM 5170 OD1 ASN H 262 -12.345 16.408 23.936 1.00 12.70 B O
ATOM 5171 ND2 ASN H 262 -10.583 15.980 25.264 1.00 13.20 B N
ATOM 5172 C ASN H 262 -11.258 18.482 21.619 1.00 10.17 B c
ATOM 5173 O ASN H 262 -12.347 18.887 22.027 1.00 10.52 B o
ATOM 5174 N ASP H 263 -10.310 19.289 21.158 1.00 10.62 B N
ATOM 5175 CA ASP H 263 -10.437 20.734 21.247 1.00 11.02 B c
ATOM 5176 CB ASP H 263 -9.057 21.395 21.285 1.00 11.49 B c
ATOM 5177 CG ASP H 263 -9.138 22.905 21.401 1.00 12.80 B c
ATOM 5178 OD1 ASP H 263 -9.972 23.401 22.188 1.00 14.72 B o
ATOM 5179 OD2 ASP H 263 -8.354 23.596 20.717 1.00 13.88 B o
ATOM 5180 C ASP H 263 -11.261 21.293 20.091 1.00 10.92 B c
ATOM 5181 O ASP H 263 -11.686 22.446 20.130 1.00 10.96 B o
ATOM 5182 N MET H 264 -11.539 20.453 19.097 1.00 10.91 B N
ATOM 5183 CA MET H 264 -12.199 20.904 17.871 1.00 10.78 E ; c
ATOM 5184 CB MET H 264 -12.091 19.840 16.770 1.00 10.51 B , c
ATOM 5185 CG MET H 264 -10.664 19.427 16.425 1.00 11.26 E ; c
ATOM 5186 SD MET H 264 -10.510 18.571 14.840 1.00 12.70 B s
ATOM 5187 CE MET H 264 -11.715 17.260 15.021 1.00 13.92 B c
ATOM 5188 C MET H 264 -13.666 21.240 18.119 1.00 10.85 B c
ATOM 5189 O MET H 264 -14.369 20.489 18.795 1.00 11.03 B o
ATOM 5190 N PRO H 265 -14.146 22.342 17.517 1.00 10.88 B N
ATOM 5191 CA PRO H 265 -15.522 22.802 17.700 1.00 11.09 B c
ATOM 5192 CB PRO H 265 -15.515 24.198 17.060 1.00 11.28 B c
ATOM 5193 CG PRO H 265 -14.322 24.216 16.167 1.00 11.24 B c
ATOM 5194 CD PRO H 265 -13.313 23.356 16.849 1.00 11.03 B c
ATOM 5195 C PRO H 265 -16.546 21.912 17.003 1.00 11.19 B c
ATOM 5196 O PRO H 265 -17.320 22.395 16.177 1.00 11.47 B o
ATOM 5197 N ILE H 266 -16.633 20.655 17.425 1.00 11.54 B N
ATOM 5198 CA ILE H 266 -17.540 19.710 16.786 1.00 12.15 B c
ATOM 5199 CB ILE H 266 -16.794 18.757 15.828 1.00 12.22 B c
ATOM 5200 CGI ILE H 266 -15.611 18.088 16.536 1.00 12.53 B c
ATOM 5201 CD1 ILE H 266 -15.044 16.895 15.789 1.00 12.40 B c ATOM 5202 CG2 ILE H 266 -16.337 19.507 14.588 1.00 12.74 B C
ATOM 5203 C ILE H 266 -18.353 18.902 17.793 1.00 12.29 B C
ATOM 5204 O ILE H 266 -18.068 18.913 18.991 1.00 12.36 B O
ATOM 5205 N TH H 267 -19.404 18.252 17.303 1.00 12.29 B N
ATOM 5206 CA THR H 267 -20.248 17.414 18.148 1.00 12.43 B C
ATOM 5207 CB THR H 267 -21.440 16.821 17.366 1.00 12.40 B C
ATOM 5208 OG1 THR H 267 -21.299 15.397 17.278 1.00 13.21 B O
ATOM 5209 CG2 THR H 267 -21.509 17.405 15.968 1.00 12.21 B C
ATOM 5210 C THR H 267 -19.432 16.276 18.740 1.00 12.37 B C
ATOM 5211 O THR H 267 -18.246 16.134 18.446 1.00 12.29 B O
ATOM 5212 N ASN H 268 -20.058 15.490 19.605 1.00 12.47 B N
ATOM 5213 CA ASN H 268 -19.325 14.501 20.377 1.00 12.57 B C
ATOM 5214 CB ASN H 268 -20.025 14.218 21.701 1.00 12.69 B C
ATOM 5215 CG ASN H 268 -19.461 15.041 22.832 1.00 13.65 B C
ATOM 5216 OD1 ASN H 268 -18.555 15.851 22.631 1.00 14.37 B O
ATOM 5217 ND2 ASN H 268 -20.005 14.856 24.028 1.00 15.74 B N
ATOM 5218 C ASN H 268 -19.084 13.207 19.621 1.00 12.43 B C
ATOM 5219 O ASN H 268 -18.038 12.576 19.776 1.00 12.51 B O
ATOM 5220 N ASP H 269 -20.107 12.747 18.912 1.00 12.34 B N
ATOM 5221 CA ASP H 269 -19.976 11.565 18.077 1.00 12.33 B C
ATOM 5222 CB ASP H 269 -21.316 11.222 17.431 1.00 12.89 B C
ATOM 5223 CG ASP H 269 -22.404 10.959 18.456 1.00 14.84 B C
ATOM 5224 OD1 ASP H 269 -22.145 10.209 19.422 1.00 16.90 B O
ATOM 5225 OD2 ASP H 269 -23.487 11.573 18.346 1.00 17.65 B O
ATOM 5226 C ASP H 269 -18.916 11.780 17.008 1.00 11.60 B C
ATOM 5227 O ASP H 269 -18.073 10.914 16.774 1.00 11.65 B O
ATOM 5228 N GLN H 270 -18.924 12.963 16.405 1.00 10.62 B N
ATOM 5229 CA GLN H 270 -17.836 13.371 15.530 1.00 10.01 B C
ATOM 5230 CB GLN H 270 -17.958 14.851 15.179 1.00 10.18 B C
ATOM 5231 CG GLN H 270 -17.709 15.154 13.718 1.00 11.49 B C
ATOM 5232 CD GLN H 270 -18.572 16.286 13.213 1.00 14.38 B C
ATOM 5233 OE1 GLN H 270 -18.076 17.238 12.613 1.00 16.38 B O
ATOM 5234 NE2 GLN H 270 -19.866 16.215 13.496 1.00 15.41 B N
ATOM 5235 C GLN H 270 -16.486 13.097 16.181 1.00 9.48 B C
ATOM 5236 O GLN H 270 -15.696 12.296 15.682 1.00 9.12 B O
ATOM 5237 N LYS H 271 -16.229 13.763 17.301 1.00 9.19 B N
ATOM 5238 CA LYS H 271 -15.004 13.541 18.056 1.00 8.89 B C
ATOM 5239 CB LYS H 271 -15.117 14.168 19.448 1.00 8.52 B C
ATOM 5240 CG LYS H 271 -15.410 15.663 19.445 1.00 9.14 B C
ATOM 5241 CD LYS H 271 -14.906 16.316 20.726 1.00 10.72 B C
ATOM 5242 CE LYS H 271 -15.469 17.718 20.900 1.00 10.79 B C
ATOM 5243 NZ LYS H 271 -14.711 18.506 21.916 1.00 9.77 B N
ATOM 5244 C LYS H 271 -14.699 12.049 18.175 1.00 8.83 B C
ATOM 5245 O LYS H 271 -13.660 11.577 17.713 1.00 9.05 B O
ATOM 5246 N LYS H 272 -15.653 11.301 18.719 1.00 8.65 B N
ATOM 5247 CA LYS H 272 -15.485 9.868 18.899 1.00 8.50 B C
ATOM 5248 CB LYS H 272 -16.766 9.240 19.443 1.00 9.14 B C
ATOM 5249 CG LYS H 272 -16.762 7.726 19.397 1.00 11.58 B C
ATOM 5250 CD LYS H 272 -18.170 7.167 19.394 1.00 15.78 B C
ATOM 5251 CE LYS H 272 -18.151 5.663 19.599 1.00 17.65 B C
ATOM 5252 NZ LYS H 272 -19.476 5.142 20.029 1.00 19.68 B N
ATOM 5253 C LYS H 272 -15.083 9.185 17.598 1.00 7.88 B C
ATOM 5254 O LYS H 272 -14.195 8.332 17.587 1.00 8.12 B O
ATOM 5255 N LEU H 273 -15.787 9.506 16.517 1.00 6.95 B N
ATOM 5256 CA LEU H 273 -15.456 8.939 15.216 1.00 5.70 B C
ATOM 5257 CB LEU H 273 -16.366 9.490 14.116 1.00 5.85 B C
ATOM 5258 CG LEU H 273 -15.894 9.204 12.683 1.00 4.65 B C
ATOM 5259 CD1 LEU H 273 -16.085 7.739 12.312 1.00 4.57 B C
ATOM 5260 CD2 LEU H 273 -16.569 10.123 11.669 1.00 3.69 B C
ATOM 5261 C LEU H 273 -14.005 9.227 14.877 1.00 5.14 B C ATOM 5262 O LEU H 273 -13.188 8.312 14.795 1.00 5.25 B O
ATOM 5263 N MET H 274 -13.668 10.509 14.775 1.00 4.52 B N
ATOM 5264 CA MET H 274 -12.307 10.910 14.447 1.00 4.59 B C
ATOM 5265 CB MET H 274 -12.147 12.429 14.567 1.00 4.35 B C
ATOM 5266 CG MET H 274 -12.862 13.219 13.479 1.00 4.50 B C
ATOM 5267 SD MET H 274 -12.547 14.992 13.574 1.00 5.51 B S
ATOM 5268 CE MET H 274 -10.875 15.078 12.935 1.00 5.26 B C
ATOM 5269 C MET H 274 -11.294 10.190 15.334 1.00 5.18 B C
ATOM 5270 O MET H 274 -10.272 9.703 14.851 1.00 5.61 B O
ATOM 5271 N SE H 275 -11.652 10.006 16.601 1.00 5.89 B N
ATOM 5272 CA SER H 275 -10.752 9.380 17.557 1.00 6.18 B C
ATOM 5273 CB SER H 275 -11.237 9.619 18.988 1.00 6.33 B C
ATOM 5274 OG SER H 275 -11.029 10.969 19.371 1.00 5.91 B O
ATOM 5275 C SER H 275 -10.583 7.886 17.288 1.00 6.58 B C
ATOM 5276 O SER H 275 -9.519 7.318 17.544 1.00 7.03 B O
ATOM 5277 N ASN H 276 -11.607 7.268 16.711 1.00 7.07 B N
ATOM 5278 CA ASN H 276 -11.525 5.857 16.369 1.00 7.86 B C
ATOM 5279 CB ASN H 276 -12.885 5.173 16.547 1.00 8.34 B C
ATOM 5280 CG ASN H 276 -13.108 4.676 17.969 1.00 9.77 B C
ATOM 5281 OD1 ASN H 276 -12.161 4.307 18.666 1.00 11.84 B O
ATOM 5282 ND2 ASN H 276 -14.351 4.748 18.433 1.00 11.15 B N
ATOM 5283 C ASN H 276 -10.959 5.605 14.971 1.00 7.71 B C
ATOM 5284 O ASN H 276 -10.950 4.468 14.498 1.00 7.84 B O
ATOM 5285 N ASN H 277 -10.386 6.643 14.363 1.00 7.77 B N
ATOM 5286 CA ASN H 277 -10.026 6.597 12.943 1.00 7.85 B C
ATOM 5287 CB ASN H 277 -11.209 7.021 12.073 1.00 7.58 B C
ATOM 5288 CG ASN H 277 -12.197 5.896 11.846 1.00 8.29 B C
ATOM 5289 OD1 ASN H 277 -11.932 4.970 11.079 1.00 9.04 B O
ATOM 5290 ND2 ASN H 277 -13.297 5.915 12.592 1.00 9.57 B N
ATOM 5291 C ASN H 277 -8.792 7.426 12.585 1.00 7.86 B C
ATOM 5292 O ASN H 277 -8.614 7.832 11.435 1.00 7.85 B O
ATOM 5293 N VAL H 278 -8.003 7.754 13.603 1.00 7.67 B N
ATOM 5294 CA VAL H 278 -6.682 8.354 13.425 1.00 7.77 B C
ATOM 5295 CB VAL H 278 -5.677 7.813 14.459 1.00 7.98 B C
ATOM 5296 CGI VAL H 278 -5.763 8.615 15.749 1.00 7.21 B C
ATOM 5297 CG2 VAL H 278 -5.932 6.336 14.725 1.00 8.99 B C
ATOM 5298 C VAL H 278 -6.095 8.223 12.019 1.00 7.76 B C
ATOM 5299 O VAL H 278 -5.641 9.211 11.444 1.00 7.84 B O
ATOM 5300 N GLN H 279 -5.935 6.989 11.553 1.00 7.47 B N
ATOM 5301 CA GLN H 279 -5.162 6.725 10.343 1.00 7.07 B C
ATOM 5302 CB GLN H 279 -5.291 5.256 9.938 1.00 7.62 B C
ATOM 5303 CG GLN H 279 -3.986 4.621 9.497 1.00 10.35 B C
ATOM 5304 CD GLN H 279 -4.194 3.335 8.725 1.00 13.70 B C
ATOM 5305 OE1 GLN H 279 -5.319 2.986 8.367 1.00 15.06 B O
ATOM 5306 NE2 GLN H 279 -3.105 2.622 8.460 1.00 13.97 B N
ATOM 5307 C GLN H 279 -5.610 7.621 9.192 1.00 6.02 B C
ATOM 5308 O GLN H 279 -4.795 8.297 8.563 1.00 5.45 B O
ATOM 5309 N ILE H 280 -6.881 7.492 8.829 1.00 5.25 B N
ATOM 5310 CA ILE H 280 -7.499 8.346 7.822 1.00 4.74 B C
ATOM 5311 CB ILE H 280 -9.022 8.133 7.775 1.00 4.58 B C
ATOM 5312 CGI ILE H 280 -9.349 6.641 7.685 1.00 4.16 B C
ATOM 5313 CD1 ILE H 280 -8.986 6.014 6.357 1.00 3.88 B C
ATOM 5314 CG2 ILE H 280 -9.636 8.897 6.612 1.00 3.92 B C
ATOM 5315 C ILE H 280 -7.225 9.818 8.101 1.00 4.43 B C
ATOM 5316 O ILE H 280 -6.655 10.522 7.268 1.00 4.39 B O
ATOM 5317 N VAL H 281 -7.745 10.301 9.224 1.00 4.05 B N
ATOM 5318 CA VAL H 281 -7.502 11.671 9.651 1.00 3.58 B C
ATOM 5319 CB VAL H 281 -7.705 11.833 11.170 1.00 3.13 B C
ATOM 5320 CGI VAL H 281 -7.901 13.299 11.526 1.00 2.34 B C
ATOM 5321 CG2 VAL H 281 -8.890 11.002 11.638 1.00 2.21 B C ATOM 5322 C VAL H 281 -6.089 12.110 9.280 1.00 3.96 B C
ATOM 5323 O VAL H 281 -5.905 13.063 8.522 1.00 4.15 B O
ATOM 5324 N A G H 282 -5.096 11.377 9.777 1.00 4.23 B N
ATOM 5325 CA ARG H 282 -3.697 11.649 9.454 1.00 4.45 B C
ATOM 5326 CB ARG H 282 -2.799 10.506 9.941 1.00 3.96 B C
ATOM 5327 CG ARG H 282 -2.843 10.255 11.440 1.00 2.99 B C
ATOM 5328 CD ARG H 282 -1.441 10.173 12.028 1.00 2.28 B C
ATOM 5329 NE ARG H 282 -1.470 9.891 13.460 1.00 2.00 B N
ATOM 5330 CZ ARG H 282 -0.687 10.483 14.358 1.00 2.44 B C
ATOM 5331 NH1 ARG H 282 0.219 11.371 13.970 1.00 2.04 B N
ATOM 5332 NH2 ARG H 282 -0.770 10.140 15.636 1.00 3.44 B N
ATOM 5333 C ARG H 282 -3.530 11.813 7.953 1.00 5.32 B C
ATOM 5334 O ARG H 282 -2.952 12.793 7.482 1.00 5.95 B O
ATOM 5335 N GLN H 283 -3.946 10.791 7.214 1.00 5.50 B N
ATOM 5336 CA GLN H 283 -3.837 10.802 5.766 1.00 5.80 B C
ATOM 5337 CB GLN H 283 -4.404 9.511 5.178 1.00 6.19 B C
ATOM 5338 CG GLN H 283 -3.531 8.297 5.431 1.00 9.68 B C
ATOM 5339 CD GLN H 283 -4.248 6.994 5.156 1.00 13.92 B C
ATOM 5340 OE1 GLN H 283 -5.408 6.984 4.745 1.00 16.20 B O
ATOM 5341 NE2 GLN H 283 -3.549 5.883 5.354 1.00 14.17 B N
ATOM 5342 C GLN H 283 -4.552 12.008 5.175 1.00 5.44 B C
ATOM 5343 O GLN H 283 -4.187 12.493 4.104 1.00 5.43 B O
ATOM 5344 N GLN H 284 -5.532 12.527 5.905 1.00 5.26 B N
ATOM 5345 CA GLN H 284 -6.361 13.609 5.396 1.00 5.18 B C
ATOM 5346 CB GLN H 284 -7.799 13.451 5.877 1.00 5.32 B C
ATOM 5347 CG GLN H 284 -8.666 12.649 4.933 1.00 6.85 B C
ATOM 5348 CD GLN H 284 -10.091 12.547 5.415 1.00 9.21 B C
ATOM 5349 OE1 GLN H 284 -10.340 12.297 6.595 1.00 9.74 B O
ATOM 5350 NE2 GLN H 284 -11.034 12.860 4.537 1.00 9.79 B N
ATOM 5351 C GLN H 284 -5.817 14.967 5.813 1.00 4.67 B C
ATOM 5352 O GLN H 284 -6.336 16.006 5.406 1.00 4.19 B O
ATOM 5353 N SER H 285 -4.758 14.950 6.614 1.00 4.51 B N
ATOM 5354 CA SER H 285 -4.240 16.170 7.212 1.00 4.39 B C
ATOM 5355 CB SER H 285 -4.020 15.979 8.713 1.00 4.13 B C
ATOM 5356 OG SER H 285 -5.177 15.446 9.334 1.00 4.40 B O
ATOM 5357 C SER H 285 -2.943 16.598 6.540 1.00 4.44 B C
ATOM 5358 O SER H 285 -2.286 15.804 5.866 1.00 4.82 B O
ATOM 5359 N TYR H 286 -2.600 17.870 6.704 1.00 4.53 B N
ATOM 5360 CA TYR H 286 -1.328 18.388 6.228 1.00 4.80 B C
ATOM 5361 CB TYR H 286 -1.560 19.527 5.236 1.00 4.88 B C
ATOM 5362 CG TYR H 286 -2.163 19.083 3.923 1.00 5.68 B C
ATOM 5363 CD1 TYR H 286 -3.448 18.558 3.868 1.00 7.34 B C
ATOM 5364 CE1 TYR H 286 -4.003 18.153 2.668 1.00 9.02 B C
ATOM 5365 CZ TYR H 286 -3.279 18.287 1.502 1.00 9.40 B C
ATOM 5366 OH TYR H 286 -3.829 17.892 0.304 1.00 10.44 B O
ATOM 5367 CE2 TYR H 286 -2.006 18.817 1.530 1.00 9.38 B C
ATOM 5368 CD2 TYR H 286 -1.458 19.214 2.735 1.00 7.39 B C
ATOM 5369 C TYR H 286 -0.501 18.884 7.404 1.00 4.76 B C
ATOM 5370 O TYR H 286 -1.036 19.160 8.478 1.00 5.25 B O
ATOM 5371 N SER H 287 0.803 19.011 7.194 1.00 4.52 B N
ATOM 5372 CA SER H 287 1.649 19.738 8.125 1.00 4.45 B C
ATOM 5373 CB SER H 287 2.518 18.768 8.927 1.00 4.57 B C
ATOM 5374 OG SER H 287 3.602 19.441 9.544 1.00 4.38 B O
ATOM 5375 C SER H 287 2.515 20.758 7.396 1.00 4.61 B C
ATOM 5376 O SER H 287 3.264 20.409 6.483 1.00 4.40 B O
ATOM 5377 N ILE H 288 2.294 22.033 7.710 1.00 5.11 B N
ATOM 5378 CA ILE H 288 3.067 23.130 7.131 1.00 5.81 B C
ATOM 5379 CB ILE H 288 2.176 24.349 6.825 1.00 5.52 B C
ATOM 5380 CGI ILE H 288 0.730 23.913 6.578 1.00 5.47 B C
ATOM 5381 CD1 ILE H 288 0.479 23.356 5.196 1.00 6.23 B C ATOM 5382 CG2 ILE H 288 2.733 25.142 5.651 1.00 6.22 B C
ATOM 5383 C ILE H 288 4.170 23.581 8.080 1.00 6.71 B C
ATOM 5384 O ILE H 288 3.902 23.948 9.224 1.00 7.30 B O
ATOM 5385 N MET H 289 5.380 23.699 7.548 1.00 7.71 B N
ATOM 5386 CA MET H 289 6.487 24.307 8.274 1.00 8.57 B C
ATOM 5387 CB MET H 289 7.781 24.096 7.492 1.00 8.71 B C
ATOM 5388 CG MET H 289 9.038 24.181 8.326 1.00 9.70 B C
ATOM 5389 SD MET H 289 10.511 24.120 7.292 1.00 12.59 B S
ATOM 5390 CE MET H 289 10.168 25.446 6.138 1.00 12.41 B C
ATOM 5391 C MET H 289 6.245 25.801 8.468 1.00 9.12 B C
ATOM 5392 O MET H 289 5.976 26.513 7.501 1.00 9.31 B O
ATOM 5393 N SE H 290 6.457 26.293 9.688 1.00 9.80 B N
ATOM 5394 CA SER H 290 6.140 27.688 10.021 1.00 10.49 B C
ATOM 5395 CB SER H 290 5.283 27.777 11.287 1.00 10.64 B C
ATOM 5396 OG SER H 290 4.906 29.117 11.560 1.00 11.99 B O
ATOM 5397 C SER H 290 7.372 28.582 10.146 1.00 10.75 B C
ATOM 5398 O SER H 290 7.635 29.401 9.265 1.00 10.89 B O
ATOM 5399 N ILE H 291 8.095 28.469 11.258 1.00 11.04 B N
ATOM 5400 CA ILE H 291 9.405 29.112 11.361 1.00 11.41 B C
ATOM 5401 CB ILE H 291 9.335 30.523 11.981 1.00 11.80 B C
ATOM 5402 CG1 ILE H 291 8.071 30.680 12.828 1.00 11.81 B C
ATOM 5403 CD1 ILE H 291 8.273 30.362 14.291 1.00 11.76 B C
ATOM 5404 CG2 ILE H 291 9.390 31.586 10.891 1.00 12.39 B C
ATOM 5405 C ILE H 291 10.510 28.289 12.022 1.00 11.13 B C
ATOM 5406 O ILE H 291 10.337 27.742 13.111 1.00 10.55 B O
ATOM 5407 N ILE H 292 11.678 28.302 11.388 1.00 11.36 B N
ATOM 5408 CA ILE H 292 12.827 27.544 11.855 1.00 11.82 B C
ATOM 5409 CB ILE H 292 13.483 26.752 10.710 1.00 11.86 B C
ATOM 5410 CGI ILE H 292 12.770 27.030 9.386 1.00 13.42 B C
ATOM 5411 CD1 ILE H 292 11.373 27.593 9.542 1.00 15.86 B C
ATOM 5412 CG2 ILE H 292 13.500 25.262 11.022 1.00 10.85 B C
ATOM 5413 C ILE H 292 13.867 28.476 12.454 1.00 11.72 B C
ATOM 5414 O ILE H 292 14.414 29.343 11.771 1.00 11.28 B O
ATOM 5415 N LYS H 293 14.150 28.269 13.733 1.00 12.11 B N
ATOM 5416 CA LYS H 293 15.287 28.894 14.382 1.00 12.92 B C
ATOM 5417 CB LYS H 293 14.812 29.763 15.544 1.00 13.15 B C
ATOM 5418 CG LYS H 293 13.615 30.634 15.208 1.00 14.17 B C
ATOM 5419 CD LYS H 293 13.793 32.037 15.758 1.00 15.37 B C
ATOM 5420 CE LYS H 293 12.940 33.041 15.001 1.00 16.68 B C
ATOM 5421 NZ LYS H 293 13.111 34.421 15.532 1.00 18.18 B N
ATOM 5422 C LYS H 293 16.224 27.813 14.894 1.00 13.32 B C
ATOM 5423 O LYS H 293 15.800 26.689 15.167 1.00 13.17 B O
ATOM 5424 N GLU H 294 17.511 28.132 14.944 1.00 14.07 B N
ATOM 5425 CA GLU H 294 18.518 27.147 15.302 1.00 15.07 B C
ATOM 5426 CB GLU H 294 19.847 27.831 15.624 1.00 15.94 B C
ATOM 5427 CG GLU H 294 20.563 28.399 14.409 1.00 19.87 B C
ATOM 5428 CD GLU H 294 21.978 28.849 14.721 1.00 23.88 B C
ATOM 5429 OE1 GLU H 294 22.830 27.983 15.010 1.00 23.75 B O
ATOM 5430 OE2 GLU H 294 22.247 30.066 14.640 1.00 25.81 B O
ATOM 5431 C GLU H 294 18.056 26.299 16.482 1.00 14.40 B C
ATOM 5432 O GLU H 294 18.348 25.106 16.546 1.00 14.33 B O
ATOM 5433 N GLU H 295 17.279 26.904 17.378 1.00 13.97 B N
ATOM 5434 CA GLU H 295 16.914 26.255 18.635 1.00 13.84 B C
ATOM 5435 CB GLU H 295 17.570 26.953 19.830 1.00 14.67 B C
ATOM 5436 CG GLU H 295 18.047 28.366 19.550 1.00 17.56 B C
ATOM 5437 CD GLU H 295 16.928 29.281 19.096 1.00 21.41 B C
ATOM 5438 OE1 GLU H 295 16.816 29.524 17.876 1.00 22.35 B O
ATOM 5439 OE2 GLU H 295 16.190 29.795 19.962 1.00 23.20 B O
ATOM 5440 C GLU H 295 15.406 26.155 18.851 1.00 12.77 B C
ATOM 5441 O GLU H 295 14.956 25.743 19.919 1.00 12.58 B O ATOM 5442 N VAL H 296 14.627 26.533 17.845 1.00 11.72 B N
ATOM 5443 CA VAL H 296 13.195 26.268 17.870 1.00 10.65 B C
ATOM 5444 CB VAL H 296 12.418 27.396 18.571 1.00 10.47 B C
ATOM 5445 CGI VAL H 296 10.974 26.983 18.804 1.00 9.77 B c
ATOM 5446 CG2 VAL H 296 13.090 27.760 19.884 1.00 11.31 B C
ATOM 5447 C VAL H 296 12.632 26.053 16.473 1.00 10.26 B c
ATOM 5448 O VAL H 296 12.887 26.838 15.561 1.00 10.09 B o
ATOM 5449 N LEU H 297 11.781 25.042 16.345 1.00 9.77 B N
ATOM 5450 CA LEU H 297 11.034 24.815 15.119 1.00 8.97 B c
ATOM 5451 CB LEU H 297 11.386 23.448 14.534 1.00 8.64 B c
ATOM 5452 CG LEU H 297 10.442 22.948 13.442 1.00 9.01 B c
ATOM 5453 CD1 LEU H 297 10.243 24.018 12.373 1.00 9.79 B c
ATOM 5454 CD2 LEU H 297 10.960 21.648 12.834 1.00 9.43 B c
ATOM 5455 C LEU H 297 9.535 24.885 15.388 1.00 8.34 B c
ATOM 5456 O LEU H 297 9.006 24.129 16.205 1.00 8.64 B o
ATOM 5457 N ALA H 298 8.848 25.771 14.675 1.00 7.21 B N
ATOM 5458 CA ALA H 298 7.396 25.872 14.777 1.00 6.33 B c
ATOM 5459 CB ALA H 298 6.987 27.268 15.238 1.00 6.68 B c
ATOM 5460 C ALA H 298 6.749 25.537 13.441 1.00 5.85 B c
ATOM 5461 O ALA H 298 7.310 25.823 12.384 1.00 5.96 B o
ATOM 5462 N TY H 299 5.653 24.793 13.492 1.00 5.28 B N
ATOM 5463 CA TY H 299 4.928 24.443 12.282 1.00 4.63 B c
ATOM 5464 CB TY H 299 5.468 23.142 11.691 1.00 4.36 B c
ATOM 5465 CG TYR H 299 5.432 21.978 12.652 1.00 4.34 B c
ATOM 5466 CD1 TYR H 299 4.330 21.136 12.711 1.00 4.48 B c
ATOM 5467 CE1 TYR H 299 4.299 20.061 13.578 1.00 4.55 B c
ATOM 5468 CZ TYR H 299 5.373 19.826 14.410 1.00 3.72 B c
ATOM 5469 OH TYR H 299 5.343 18.762 15.282 1.00 2.38 B o
ATOM 5470 CE2 TYR H 299 6.475 20.651 14.374 1.00 4.13 B c
ATOM 5471 CD2 TYR H 299 6.494 21.727 13.509 1.00 4.38 B c
ATOM 5472 C TYR H 299 3.443 24.308 12.563 1.00 4.32 B c
ATOM 5473 O TYR H 299 3.034 24.068 13.699 1.00 4.67 B o
ATOM 5474 N VAL H 300 2.638 24.454 11.519 1.00 3.87 B N
ATOM 5475 CA VAL H 300 1.193 24.395 11.664 1.00 3.57 B c
ATOM 5476 CB VAL H 300 0.501 25.518 10.873 1.00 3.52 B c
ATOM 5477 CGI VAL H 300 -0.990 25.241 10.751 1.00 3.44 B c
ATOM 5478 CG2 VAL H 300 0.743 26.861 11.544 1.00 3.90 B c
ATOM 5479 C VAL H 300 0.654 23.049 11.203 1.00 3.53 B c
ATOM 5480 O VAL H 300 0.858 22.647 10.058 1.00 3.68 B o
ATOM 5481 N VAL H 301 -0.061 22.370 12.092 1.00 3.41 B N
ATOM 5482 CA VAL H 301 -0.857 21.216 11.704 1.00 3.36 B c
ATOM 5483 CB VAL H 301 -1.038 20.233 12.873 1.00 3.24 B c
ATOM 5484 CGI VAL H 301 -2.141 19.235 12.559 1.00 3.76 B c
ATOM 5485 CG2 VAL H 301 0.270 19.516 13.169 1.00 3.10 B c
ATOM 5486 C VAL H 301 -2.223 21.641 11.183 1.00 3.48 B c
ATOM 5487 O VAL H 301 -2.772 22.661 11.602 1.00 3.92 B o
ATOM 5488 N GLN H 302 -2.766 20.845 10.270 1.00 3.21 B N
ATOM 5489 CA GLN H 302 -3.989 21.201 9.569 1.00 3.01 B c
ATOM 5490 CB GLN H 302 -3.662 21.767 8.188 1.00 3.24 B c
ATOM 5491 CG GLN H 302 -4.875 21.992 7.307 1.00 5.21 B c
ATOM 5492 CD GLN H 302 -4.603 22.977 6.191 1.00 7.54 B c
ATOM 5493 OE1 GLN H 302 -3.715 23.822 6.297 1.00 7.28 B o
ATOM 5494 NE2 GLN H 302 -5.364 22.870 5.108 1.00 9.27 B N
ATOM 5495 C GLN H 302 -4.885 19.978 9.434 1.00 2.42 B c
ATOM 5496 O GLN H 302 -4.564 19.038 8.706 1.00 2.40 B o
ATOM 5497 N LEU H 303 -5.964 19.959 10.207 1.00 2.00 B N
ATOM 5498 CA LEU H 303 -6.802 18.775 10.329 1.00 2.00 B c
ATOM 5499 CB LEU H 303 -6.945 18.389 11.802 1.00 2.00 B c
ATOM 5500 CG LEU H 303 -5.634 18.464 12.590 1.00 2.00 B c
ATOM 5501 CD1 LEU H 303 -5.840 18.189 14.073 1.00 2.00 B c ATOM 5502 CD2 LEU H 303 -4.598 17.517 11.999 1.00 2.00 B C
ATOM 5503 C LEU H 303 -8.172 19.024 9.704 1.00 2.00 B C
ATOM 5504 O LEU H 303 -8.499 20.159 9.359 1.00 2.45 B O
ATOM 5505 N PRO H 304 -8.955 17.949 9.506 1.00 2.00 B N
ATOM 5506 CA PRO H 304 -10.222 18.040 8.763 1.00 2.07 B C
ATOM 5507 CB PRO H 304 -10.407 16.623 8.206 1.00 2.00 B C
ATOM 5508 CG PRO H 304 -9.560 15.748 9.074 1.00 2.00 B C
ATOM 5509 CD PRO H 304 -8.390 16.589 9.469 1.00 2.06 B C
ATOM 5510 C PRO H 304 -11.449 18.462 9.590 1.00 2.11 B C
ATOM 5511 O PRO H 304 -11.353 18.606 10.812 1.00 2.13 B O
ATOM 5512 N ALA H 305 -12.622 18.425 8.953 1.00 30.00 B N
ATOM 5513 CA ALA H 305 -12.858 19.173 7.708 1.00 30.00 B C
ATOM 5514 CB ALA H 305 -11.532 19.487 7.023 1.00 30.00 B C
ATOM 5515 C ALA H 305 -13.809 18.445 6.733 1.00 30.00 B C
ATOM 5516 O ALA H 305 -13.601 17.265 6.429 1.00 30.00 B O
ATOM 5517 N TYR H 306 -14.925 19.101 6.370 1.00 13.49 B N
ATOM 5518 CA TYR H 306 -15.658 18.816 5.101 1.00 13.70 B C
ATOM 5519 CB TYR H 306 -16.947 18.016 5.303 1.00 13.93 B C
ATOM 5520 CG TYR H 306 -17.614 18.033 6.640 1.00 14.08 B C
ATOM 5521 CD1 TYR H 306 -18.719 18.859 6.857 1.00 14.59 B C
ATOM 5522 CE1 TYR H 306 -19.825 18.384 7.554 1.00 14.82 B C
ATOM 5523 CZ TYR H 306 -19.818 17.083 8.031 1.00 14.52 B C
ATOM 5524 OH TYR H 306 -20.780 16.679 8.925 1.00 13.02 B O
ATOM 5525 CE2 TYR H 306 -18.727 16.282 7.818 1.00 15.22 B C
ATOM 5526 CD2 TYR H 306 -17.583 16.855 7.363 1.00 14.61 B C
ATOM 5527 C TYR H 306 -16.111 19.916 4.144 1.00 13.68 B C
ATOM 5528 O TYR H 306 -15.500 20.982 4.051 1.00 13.95 B O
ATOM 5529 N GLY H 307 -17.412 19.756 3.831 1.00 13.54 B N
ATOM 5530 CA GLY H 307 -18.190 20.428 2.747 1.00 13.37 B C
ATOM 5531 C GLY H 307 -18.295 19.776 1.353 1.00 13.47 B C
ATOM 5532 O GLY H 307 -17.282 19.701 0.658 1.00 13.90 B O
ATOM 5533 N VAL H 308 -19.505 19.569 0.815 1.00 13.31 B N
ATOM 5534 CA VAL H 308 -19.608 19.371 -0.649 1.00 13.30 B C
ATOM 5535 CB VAL H 308 -18.352 18.643 -1.188 1.00 13.03 B C
ATOM 5536 CGI VAL H 308 -17.948 19.190 -2.545 1.00 13.62 B C
ATOM 5537 CG2 VAL H 308 -17.209 18.740 -0.205 1.00 12.86 B C
ATOM 5538 C VAL H 308 -20.720 18.501 -1.196 1.00 13.58 B C
ATOM 5539 O VAL H 308 -21.809 18.418 -0.627 1.00 13.71 B o
ATOM 5540 N ILE H 309 -20.173 17.489 - 1.845 1.00 4.08 B N
ATOM 5541 CA ILE H 309 -19.600 16.440 -1.057 1.00 4.84 B C
ATOM 5542 CB ILE H 309 -19.530 16.902 0.426 1.00 4.89 B c
ATOM 5543 CGI ILE H 309 -18.554 18.070 0.585 1.00 5.85 B c
ATOM 5544 CD1 ILE H 309 -17.312 17.711 1.373 1.00 8.12 B c
ATOM 5545 CG2 ILE H 309 -19.121 15.756 1.332 1.00 4.44 B c
ATOM 5546 C ILE H 309 -20.750 15.497 - 1.251 1.00 5.23 B c
ATOM 5547 O ILE H 309 -21.670 15.818 - 1.998 1.00 5.92 B o
ATOM 5548 N ASP H 310 -20.752 14.358 -0.584 1.00 5.33 B N
ATOM 5549 CA ASP H 310 -21.992 13.604 -0.482 1.00 5.83 B c
ATOM 5550 CB ASP H 310 -23.072 14.462 0.188 1.00 6.21 B c
ATOM 5551 CG ASP H 310 -22.698 14.894 1.595 1.00 7.19 B c
ATOM 5552 OD1 ASP H 310 -22.903 16.084 ■ 1.920 1.00 7.74 B o
ATOM 5553 OD2 ASP H 310 -22.425 14.005 1 2.428 1.00 7.58 B o
ATOM 5554 C ASP H 310 -22.524 13.115 ■ -1.841 1.00 6.02 B c
ATOM 5555 O ASP H 310 -23.670 12.673 -1.927 1.00 6.05 B o
ATOM 5556 N THR H 311 -21.716 13.207 -2.897 1.00 6.24 B N
ATOM 5557 CA THR H 311 -22.015 12.488 -4.140 1.00 6.14 B c
ATOM 5558 CB THR H 311 -21.097 12.933 -5.305 1.00 5.69 B c
ATOM 5559 OG1 THR H 311 -20.497 14.196 -4.994 1.00 5.34 B O ATOM 5560 CG2 THR H 311 -21.891 13.063 -6.599 1.00 7.10 B C ATOM 5561 C THR H 311 -21.832 10.990 -3.911 1.00 6.78 B C ATOM 5562 O TH H 311 -20.946 10.587 -3.160 1.00 7.33 B O
ATOM 5563 N PRO H 312 -22.611 10.155 -4.621 1.00 7.00 B N
ATOM 5564 CA PRO H 312 -22.351 8.718 -4.567 1.00 7.23 B C
ATOM 5565 CB PRO H 312 -23.560 8.115 -5.289 1.00 7.00 B C
ATOM 5566 CG PRO H 312 -24.053 9.200 -6.178 1.00 6.59 B C
ATOM 5567 CD PRO H 312 -23.800 10.475 -5.432 1.00 6.99 B C
ATOM 5568 C PRO H 312 -21.061 8.352 -5.298 1.00 7.69 B C
ATOM 5569 O PRO H 312 -20.796 8.881 -6.377 1.00 7.55 B O
ATOM 5570 N CYS H 313 -20.259 7.469 -4.712 1.00 8.10 B N
ATOM 5571 CA CYS H 313 -19.271 6.730 -5.491 1.00 8.54 B C
ATOM 5572 CB CYS H 313 -17.840 7.078 -5.071 1.00 8.77 B C
ATOM 5573 SG CYS H 313 -17.635 8.680 -4.269 1.00 10.74 B S
ATOM 5574 C CYS H 313 -19.470 5.222 -5.446 1.00 8.19 B C
ATOM 5575 O CYS H 313 -20.334 4.712 -4.734 1.00 8.07 B O
ATOM 5576 N TRP H 314 -18.571 4.517 -6.121 1.00 7.93 B N
ATOM 5577 CA TRP H 314 -18.564 3.067 -6.116 1.00 7.80 B C
ATOM 5578 CB TRP H 314 -19.648 2.528 -7.050 1.00 8.13 B C
ATOM 5579 CG TRP H 314 -19.582 3.091 -8.436 1.00 9.09 B C
ATOM 5580 CD1 TRP H 314 -19.041 2.490 -9.536 1.00 10.26 B C
ATOM 5581 NE1 TRP H 314 -19.247 3.268 -10.650 1.00 10.86 B N
ATOM 5582 CE2 TRP H 314 -19.940 4.392 -10.285 1.00 10.68 B C
ATOM 5583 CD2 TRP H 314 -20.172 4.313 -8.897 1.00 10.49 B C
ATOM 5584 CE3 TRP H 314 -20.877 5.347 -8.271 1.00 11.67 B C
ATOM 5585 CZ3 TRP H 314 -21.301 6.419 -9.037 1.00 12.98 B C
ATOM 5586 CH2 TRP H 314 -21.048 6.472 -10.413 1.00 12.74 B C
ATOM 5587 CZ2 TRP H 314 -20.369 5.472 -11.054 1.00 11.73 B C
ATOM 5588 C TRP H 314 -17.198 2.576 -6.563 1.00 7.34 B C
ATOM 5589 O TRP H 314 -16.485 3.272 -7.288 1.00 7.47 B O
ATOM 5590 N LYS H 315 -16.791 1.426 -6.041 1.00 6.75 B N
ATOM 5591 CA LYS H 315 -15.547 0.807 -6.462 1.00 6.37 B C
ATOM 5592 CB LYS H 315 -14.741 0.337 -5.252 1.00 6.38 B C
ATOM 5593 CG LYS H 315 -13.277 0.071 -5.554 1.00 6.55 B C
ATOM 5594 CD LYS H 315 -12.509 -0.282 -4.292 1.00 8.01 B C
ATOM 5595 CE LYS H 315 -11.014 -0.331 -4.556 1.00 8.78 B C
ATOM 5596 NZ LYS H 315 -10.337 -1.364 -3.726 1.00 10.21 B N
ATOM 5597 C LYS H 315 -15.825 -0.361 -7.392 1.00 6.32 B C
ATOM 5598 O LYS H 315 -16.746 -1.145 -7.164 1.00 6.21 B O
ATOM 5599 N LEU H 316 -15.089 -0.411 -8.495 1.00 6.58 B N
ATOM 5600 CA LEU H 316 -15.304 -1.435 -9.502 1.00 7.02 B C
ATOM 5601 CB LEU H 316 -15.491 -0.801 -10.880 1.00 6.64 B C
ATOM 5602 CG LEU H 316 -15.452 -1.767 -12.065 1.00 6.21 B C
ATOM 5603 CD1 LEU H 316 -16.540 -2.822 -11.936 1.00 5.94 B C
ATOM 5604 CD2 LEU H 316 -15.590 -1.011 -13.378 1.00 6.57 B C
ATOM 5605 C LEU H 316 -14.138 -2.409 -9.525 1.00 7.77 B C
ATOM 5606 O LEU H 316 -12.999 -2.024 -9.792 1.00 8.47 B O
ATOM 5607 N HIS H 317 -14.414 -3.656 -9.168 1.00 8.05 B N
ATOM 5608 CA HIS H 317 -13.460 -4.725 -9.388 1.00 8.21 B C
ATOM 5609 CB HIS H 317 -13.266 -5.547 -8.116 1.00 9.04 B C
ATOM 5610 CG HIS H 317 -13.449 -4.761 -6.856 1.00 11.41 B C
ATOM 5611 ND1 HIS H 317 -12.392 -4.368 -6.063 1.00 13.62 B N
ATOM 5612 CE1 HIS H 317 -12.854 -3.746 -4.993 1.00 14.91 B C
ATOM 5613 NE2 HIS H 317 -14.172 -3.725 -5.060 1.00 14.25 B N
ATOM 5614 CD2 HIS H 317 -14.570 -4.352 -6.216 1.00 12.67 B C
ATOM 5615 C HIS H 317 -13.904 -5.625 -10.528 1.00 7.39 B C
ATOM 5616 O HIS H 317 -15.085 -5.677 -10.870 1.00 7.23 B O
ATOM 5617 N THR H 318 -12.976 -6.451 -10.993 1.00 7.11 B N
ATOM 5618 CA THR H 318 -12.973 -6.913 -12.372 1.00 6.56 B C
ATOM 5619 CB THR H 318 -12.242 -5.919 -13.295 1.00 6.28 B C
ATOM 5620 OG1 THR H 318 -13.197 -5.193 -14.078 1.00 6.33 B O
ATOM 5621 CG2 THR H 318 -11.296 -6.662 -14.224 1.00 6.52 B C ATOM 5622 C TH H 318 -12.254 -8.251 -12.438 1.00 6.58 B C
ATOM 5623 O THR H 318 -11.142 -8.393 -11.930 1.00 6.67 B O
ATOM 5624 N SER H 319 -12.919 -9.252 -13.001 1.00 6.81 B N
ATOM 5625 CA SER H 319 -12.328 -10.578 -13.115 1.00 7.31 B C
ATOM 5626 CB SER H 319 -12.902 -11.513 -12.047 1.00 7.14 B C
ATOM 5627 OG SER H 319 -12.244 -12.769 -12.052 1.00 6.84 B O
ATOM 5628 C SER H 319 -12.533 -11.169 -14.509 1.00 7.93 B C
ATOM 5629 O SER H 319 -13.583 -10.975 -15.124 1.00 8.65 B O
ATOM 5630 N PRO H 320 -11.534 -11.917 -15.002 1.00 8.08 B N
ATOM 5631 CA PRO H 320 -11.592 -12.459 -16.354 1.00 8.34 B C
ATOM 5632 CB PRO H 320 -10.339 -13.342 -16.442 1.00 7.99 B C
ATOM 5633 CG PRO H 320 -9.773 -13.404 -15.045 1.00 8.01 B C
ATOM 5634 CD PRO H 320 -10.230 -12.163 -14.367 1.00 8.10 B C
ATOM 5635 C PRO H 320 -12.848 -13.288 -16.610 1.00 9.03 B C
ATOM 5636 O PRO H 320 -13.372 -13.928 -15.697 1.00 8.74 B O
ATOM 5637 N LEU H 321 -13.224 -13.384 -17.881 1.00 10.31 B N
ATOM 5638 CA LEU H 321 -14.514 -13.933 -18.284 1.00 11.63 B C
ATOM 5639 CB LEU H 321 -15.543 -12.807 -18.448 1.00 11.31 B C
ATOM 5640 CG LEU H 321 -17.032 -13.163 -18.454 1.00 10.97 B C
ATOM 5641 CD1 LEU H 321 -17.828 -12.071 -19.154 1.00 10.04 B C
ATOM 5642 CD2 LEU H 321 -17.273 -14.514 -19.113 1.00 10.69 B C
ATOM 5643 C LEU H 321 -14.359 -14.687 -19.603 1.00 12.92 B C
ATOM 5644 O LEU H 321 -13.871 -14.135 -20.591 1.00 13.29 B O
ATOM 5645 N CYS H 322 -14.788 -15.947 -19.611 1.00 13.39 B N
ATOM 5646 CA CYS H 322 -14.579 -16.836 -20.751 1.00 14.16 B C
ATOM 5647 CB CYS H 322 -13.459 -17.833 -20.451 1.00 13.72 B C
ATOM 5648 SG CYS H 322 -11.996 -17.091 -19.704 1.00 13.42 B S
ATOM 5649 C CYS H 322 -15.859 -17.589 -21.115 1.00 15.46 B C
ATOM 5650 O CYS H 322 -16.561 -18.099 -20.241 1.00 15.94 B O
ATOM 5651 N THR H 323 -16.097 -17.735 -22.415 1.00 16.70 B N
ATOM 5652 CA THR H 323 -17.059 -18.703 -22.940 1.00 17.84 B C
ATOM 5653 CB THR H 323 -17.054 -18.690 -24.477 1.00 17.50 B C
ATOM 5654 OG1 THR H 323 -15.767 -18.268 -24.947 1.00 15.70 B O
ATOM 5655 CG2 THR H 323 -18.118 -17.740 -25.005 1.00 18.05 B C
ATOM 5656 C THR H 323 -16.755 -20.125 -22.469 1.00 19.54 B C
ATOM 5657 O THR H 323 -15.670 -20.389 -21.950 1.00 19.84 B O
ATOM 5658 N THR H 324 -17.625 -21.068 -22.825 1.00 21.17 B N
ATOM 5659 CA THR H 324 -17.251 -22.481 -22.774 1.00 22.89 B C
ATOM 5660 CB THR H 324 -17.589 -23.138 -21.426 1.00 22.69 B C
ATOM 5661 OG1 THR H 324 -18.025 -22.141 -20.494 1.00 22.10 B O
ATOM 5662 CG2 THR H 324 -16.365 -23.854 -20.871 1.00 22.03 B C
ATOM 5663 C THR H 324 -17.737 -23.375 -23.915 1.00 24.39 B C
ATOM 5664 O THR H 324 -17.251 -24.495 -24.070 1.00 24.53 B O
ATOM 5665 N ASN H 325 -18.633 -22.866 -24.755 1.00 25.72 B N
ATOM 5666 CA ASN H 325 -18.864 -23.475 -26.064 1.00 27.01 B C
ATOM 5667 CB ASN H 325 -19.924 -24.578 -25.977 1.00 27.37 B C
ATOM 5668 CG ASN H 325 -19.337 -25.925 -25.593 1.00 28.46 B C
ATOM 5669 OD1 ASN H 325 -19.134 -26.792 -26.443 1.00 30.37 B O
ATOM 5670 ND2 ASN H 325 -19.086 -26.114 -24.303 1.00 28.78 B N
ATOM 5671 C ASN H 325 -19.246 -22.460 -27.136 1.00 27.36 B C
ATOM 5672 O ASN H 325 -19.634 -21.334 -26.829 1.00 27.94 B O
ATOM 5673 N SER H 330 -15.365 -21.167 -24.863 1.00 35.76 B N
ATOM 5674 CA SER H 330 -14.200 -21.669 -25.580 1.00 35.01 B C
ATOM 5675 CB SER H 330 -14.630 -22.631 -26.690 1.00 35.47 B C
ATOM 5676 OG SER H 330 -15.521 -22.000 -27.595 1.00 33.31 B O
ATOM 5677 C SER H 330 -13.383 -20.522 -26.168 1.00 34.35 B C
ATOM 5678 O SER H 330 -13.938 -19.509 -26.593 1.00 34.33 B O
ATOM 5679 N ASN H 331 -12.062 -20.653 -26.123 1.00 32.48 B N
ATOM 5680 CA ASN H 331 -11.191 -19.933 -27.046 1.00 30.72 B C
ATOM 5681 CB ASN H 331 -11.577 -20.233 -28.504 1.00 31.31 B C ATOM 5682 CG ASN H 331 -11.276 -21.670 -28.918 1.00 32.11 B C
ATOM 5683 OD1 ASN H 331 -10.553 -22.391 -28.229 1.00 32.54 B O
ATOM 5684 ND2 ASN H 331 -11.753 -22.055 -30.097 1.00 31.30 B N
ATOM 5685 C ASN H 331 -11.120 -18.411 -26.826 1.00 28.71 B C
ATOM 5686 O ASN H 331 -10.495 -17.710 -27.621 1.00 29.07 B O
ATOM 5687 N ILE H 332 -11.797 -17.887 -25.802 1.00 25.44 B N
ATOM 5688 CA ILE H 332 -11.904 -16.424 -25.638 1.00 21.83 B C
ATOM 5689 CB ILE H 332 -12.919 -15.806 -26.624 1.00 21.42 B C
ATOM 5690 CGI ILE H 332 -12.916 -14.280 -26.511 1.00 19.89 B C
ATOM 5691 CD 1 ILE H 332 -11.986 -13.596 -27.488 1.00 17.67 B C
ATOM 5692 CG2 ILE H 332 -14.314 -16.360 -26.374 1.00 20.61 B C
ATOM 5693 C ILE H 332 -12.204 -15.918 -24.217 1.00 20.37 B C
ATOM 5694 O ILE H 332 -13.219 -16.290 -23.624 1.00 19.95 B O
ATOM 5695 N CYS H 333 -11.425 -14.935 -23.761 1.00 18.27 B N
ATOM 5696 CA CYS H 333 -11.681 -14.282 -22.474 1.00 16.47 B C
ATOM 5697 CB CYS H 333 -10.802 -14.873 -21.371 1.00 16.14 B C
ATOM 5698 SG CYS H 333 -10.807 -16.672 -21.295 1.00 17.09 B S
ATOM 5699 C CYS H 333 -11.542 -12.763 -22.482 1.00 15.73 B C
ATOM 5700 O CYS H 333 -10.707 -12.206 -23.197 1.00 15.43 B O
ATOM 5701 N LEU H 334 -12.154 -12.155 -21.470 1.00 15.06 B N
ATOM 5702 CA LEU H 334 -12.256 -10.708 -21.353 1.00 13.79 B C
ATOM 5703 CB LEU H 334 -13.702 -10.264 -21.588 1.00 13.39 B C
ATOM 5704 CG LEU H 334 -14.262 -10.341 -23.008 1.00 13.93 B C
ATOM 5705 CD1 LEU H 334 -15.276 -9.230 -23.235 1.00 14.20 B C
ATOM 5706 CD2 LEU H 334 -13.143 -10.266 -24.035 1.00 14.52 B C
ATOM 5707 C LEU H 334 -11.868 -10.345 -19.930 1.00 13.22 B C
ATOM 5708 O LEU H 334 -12.324 -10.980 -18.980 1.00 13.31 B O
ATOM 5709 N TH H 335 -11.141 -9.246 -19.776 1.00 12.58 B N
ATOM 5710 CA THR H 335 -11.033 -8.596 -18.478 1.00 12.17 B C
ATOM 5711 CB THR H 335 -9.677 -8.904 -17.798 1.00 12.02 B C
ATOM 5712 OG1 THR H 335 -9.207 -10.191 -18.219 1.00 12.64 B O
ATOM 5713 CG2 THR H 335 -9.817 -8.893 -16.280 1.00 11.47 B C
ATOM 5714 C THR H 335 -11.203 -7.092 -18.639 1.00 11.97 B C
ATOM 5715 O THR H 335 -10.637 -6.493 -19.553 1.00 11.93 B O
ATOM 5716 N ARG H 336 -12.130 -6.526 -17.874 1.00 11.60 B N
ATOM 5717 CA ARG H 336 -12.411 -5.098 -17.949 1.00 12.15 B C
ATOM 5718 CB ARG H 336 -13.716 -4.767 -17.215 1.00 12.16 B C
ATOM 5719 CG ARG H 336 -14.525 -3.643 -17.849 1.00 12.67 B C
ATOM 5720 CD ARG H 336 -15.993 -4.018 -17.970 1.00 12.52 B C
ATOM 5721 NE ARG H 336 -16.736 -3.718 -16.750 1.00 12.35 B N
ATOM 5722 CZ ARG H 336 -17.058 -2.490 -16.355 1.00 12.54 B C
ATOM 5723 NH1 ARG H 336 -16.665 -1.439 -17.062 1.00 12.38 B N
ATOM 5724 NH2 ARG H 336 -17.761 -2.312 -15.246 1.00 12.48 B N
ATOM 5725 C ARG H 336 -11.252 -4.295 -17.361 1.00 12.71 B C
ATOM 5726 O ARG H 336 -10.891 -4.475 -16.198 1.00 12.62 B O
ATOM 5727 N THR H 337 -10.615 -3.475 -18.192 1.00 13.70 B N
ATOM 5728 CA THR H 337 -9.431 -2.733 -17.766 1.00 14.91 B C
ATOM 5729 CB THR H 337 -8.736 -2.032 -18.949 1.00 15.27 B C
ATOM 5730 OG1 THR H 337 -8.620 -2.946 -20.046 1.00 16.65 B O
ATOM 5731 CG2 THR H 337 -7.347 -1.560 -18.546 1.00 15.94 B C
ATOM 5732 C THR H 337 -9.759 -1.707 -16.681 1.00 15.16 B C
ATOM 5733 O THR H 337 -9.100 -1.659 -15.643 1.00 15.60 B O
ATOM 5734 N ASP H 338 -10.770 -0.880 -16.934 1.00 15.15 B N
ATOM 5735 CA ASP H 338 -10.988 0.325 -16.143 1.00 15.52 B C
ATOM 5736 CB ASP H 338 -11.999 1.250 -16.828 1.00 16.81 B C
ATOM 5737 CG ASP H 338 -13.028 0.489 -17.642 1.00 20.57 B C
ATOM 5738 OD1 ASP H 338 -13.670 1.103 -18.519 1.00 23.00 B O
ATOM 5739 OD2 ASP H 338 -13.224 -0.716 -17.378 1.00 22.92 B O
ATOM 5740 C ASP H 338 -11.453 -0.022 -14.733 1.00 14.21 B C
ATOM 5741 O ASP H 338 -12.651 -0.171 -14.482 1.00 14.00 B O ATOM 5742 N A G H 339 -10.494 -0.189 -13.827 1.00 12.79 B N
ATOM 5743 CA ARG H 339 -10.792 -0.528 -12.440 1.00 11.71 B C
ATOM 5744 CB ARG H 339 -9.866 -1.630 -11.950 1.00 11.73 B C
ATOM 5745 CG ARG H 339 -9.941 -2.905 -12.727 1.00 12.49 B C
ATOM 5746 CD ARG H 339 -9.329 -3.991 -11.895 1.00 13.24 B C
ATOM 5747 NE ARG H 339 -8.677 -5.006 -12.705 1.00 12.04 B N
ATOM 5748 CZ ARG H 339 -8.332 -6.200 -12.239 1.00 11.74 B C
ATOM 5749 NH1 ARG H 339 -8.540 -6.498 -10.964 1.00 13.43 B N
ATOM 5750 NH2 ARG H 339 -7.784 -7.097 -13.045 1.00 9.80 B N
ATOM 5751 C ARG H 339 -10.626 0.666 -11.519 1.00 11.16 B C
ATOM 5752 O ARG H 339 -9.690 1.448 -11.681 1.00 11.37 B O
ATOM 5753 N GLY H 340 -11.290 0.573 -10.373 1.00 10.43 B N
ATOM 5754 CA GLY H 340 -11.038 1.481 -9.269 1.00 9.52 B C
ATOM 5755 C GLY H 340 -12.279 2.268 -8.916 1.00 8.80 B C
ATOM 5756 O GLY H 340 -13.397 1.759 -8.996 1.00 8.56 B O
ATOM 5757 N TRP H 341 -12.077 3.513 -8.506 1.00 8.25 B N
ATOM 5758 CA TRP H 341 -13.156 4.309 -7.953 1.00 7.98 B C
ATOM 5759 CB TRP H 341 -12.629 5.235 -6.865 1.00 7.79 B C
ATOM 5760 CG TRP H 341 -12.435 4.538 -5.579 1.00 7.67 B C
ATOM 5761 CD1 TRP H 341 -11.275 3.990 -5.119 1.00 8.12 B C
ATOM 5762 NE1 TRP H 341 -11.496 3.346 -3.928 1.00 8.60 B N
ATOM 5763 CE2 TRP H 341 -12.834 3.401 -3.639 1.00 7.57 B C
ATOM 5764 CD2 TRP H 341 -13.464 4.093 -4.691 1.00 7.52 B C
ATOM 5765 CE3 TRP H 341 -14.848 4.291 -4.636 1.00 7.86 B C
ATOM 5766 CZ3 TRP H 341 -15.545 3.797 -3.548 1.00 7.14 B C
ATOM 5767 CH2 TRP H 341 -14.890 3.105 -2.522 1.00 6.39 B C
ATOM 5768 CZ2 TRP H 341 -13.538 2.903 -2.546 1.00 7.30 B C
ATOM 5769 C TRP H 341 -13.835 5.117 -9.037 1.00 8.26 B C
ATOM 5770 O TRP H 341 -13.222 5.978 -9.666 1.00 8.35 B O
ATOM 5771 N TYR H 342 -15.113 4.840 -9.244 1.00 8.44 B N
ATOM 5772 CA TYR H 342 -16.000 5.809 -9.847 1.00 8.53 B C
ATOM 5773 CB TYR H 342 -16.948 5.116 -10.814 1.00 8.43 B C
ATOM 5774 CG TYR H 342 -16.214 4.338 -11.870 1.00 9.17 B C
ATOM 5775 CD 1 TYR H 342 -15.551 3.163 -11.540 1.00 10.32 B C
ATOM 5776 CE1 TYR H 342 -14.766 2.503 -12.465 1.00 10.99 B C
ATOM 5777 CZ TYR H 342 -14.566 3.063 -13.709 1.00 11.00 B C
ATOM 5778 OH TYR H 342 -13.828 2.387 -14.653 1.00 12.82 B O
ATOM 5779 CE2 TYR H 342 -15.115 4.288 -14.019 1.00 10.67 B C
ATOM 5780 CD2 TYR H 342 -15.913 4.930 -13.091 1.00 10.41 B C
ATOM 5781 C TYR H 342 -16.781 6.535 -8.778 1.00 8.64 B C
ATOM 5782 O TYR H 342 -16.830 6.103 -7.628 1.00 8.40 B O
ATOM 5783 N CYS H 343 -17.373 7.657 -9.157 1.00 8.87 B N
ATOM 5784 CA CYS H 343 -17.812 8.625 -8.178 1.00 9.35 B C
ATOM 5785 CB CYS H 343 -16.702 8.901 -7.160 1.00 9.17 B C
ATOM 5786 SG CYS H 343 -17.204 9.963 -5.787 1.00 11.88 B S
ATOM 5787 C CYS H 343 -18.258 9.907 -8.863 1.00 9.42 B C
ATOM 5788 O CYS H 343 -17.552 10.444 -9.717 1.00 9.96 B O
ATOM 5789 N ASP H 344 -19.523 10.250 -8.643 1.00 9.36 B N
ATOM 5790 CA ASP H 344 -20.231 11.213 -9.477 1.00 9.24 B C
ATOM 5791 CB ASP H 344 -21.712 11.250 -9.097 1.00 9.34 B C
ATOM 5792 CG ASP H 344 -22.555 10.320 -9.943 1.00 10.72 B C
ATOM 5793 OD1 ASP H 344 -22.582 10.500 -11.178 1.00 13.93 B O
ATOM 5794 OD2 ASP H 344 -23.246 9.453 -9.367 1.00 11.87 B O
ATOM 5795 C ASP H 344 -19.632 12.607 -9.330 1.00 9.09 B C
ATOM 5796 O ASP H 344 -19.454 13.101 -8.216 1.00 9.39 B O
ATOM 5797 N ASN H 345 -19.416 13.274 -10.457 1.00 9.13 B N
ATOM 5798 CA ASN H 345 -19.165 14.709 -10.461 1.00 9.52 B C
ATOM 5799 CB ASN H 345 -17.833 15.011 -11.149 1.00 9.61 B C
ATOM 5800 CG ASN H 345 -17.166 16.258 -10.606 1.00 9.21 B C
ATOM 5801 OD1 ASN H 345 -16.787 16.316 -9.437 1.00 6.21 B O ATOM 5802 ND2 ASN H 345 -17.023 17.268 -11.456 1.00 11.05 B N
ATOM 5803 C ASN H 345 -20.303 15.452 -11.152 1.00 10.06 B C
ATOM 5804 O ASN H 345 -21.347 14.867 -11.441 1.00 11.10 B o
ATOM 5805 N ALA H 346 -20.133 16.755 -11.352 1.00 9.74 B N
ATOM 5806 CA ALA H 346 -21.211 17.584 -11.877 1.00 9.58 B C
ATOM 5807 CB ALA H 346 -20.708 18.991 -12.164 1.00 9.60 B c
ATOM 5808 C ALA H 346 -21.825 16.968 -13.133 1.00 9.66 B c
ATOM 5809 O ALA H 346 -21.347 17.196 -14.244 1.00 9.39 B o
ATOM 5810 N GLY H 347 -22.883 16.182 -12.948 1.00 10.04 B N
ATOM 5811 CA GLY H 347 -23.684 15.689 -14.067 1.00 10.68 B , c
ATOM 5812 C GLY H 347 -22.964 14.606 -14.846 1.00 10.90 B c
ATOM 5813 O GLY H 347 -23.490 14.064 -15.819 1.00 11.46 B o
ATOM 5814 N SE H 348 -21.714 14.370 -14.467 1.00 10.30 B N
ATOM 5815 CA SE H 348 -20.844 13.436 -15.165 1.00 9.94 B c
ATOM 5816 CB SE H 348 -19.833 14.200 -16.022 1.00 9.88 B c
ATOM 5817 OG SE H 348 -20.488 15.064 -16.934 1.00 10.09 B o
ATOM 5818 C SER H 348 -20.120 12.619 -14.104 1.00 9.60 B c
ATOM 5819 O SER H 348 -20.367 12.796 -12.912 1.00 9.59 B o
ATOM 5820 N VAL H 349 -19.286 11.677 -14.528 1.00 9.54 B N
ATOM 5821 CA VAL H 349 -18.647 10.766 -13.581 1.00 9.56 B c
ATOM 5822 CB VAL H 349 -19.075 9.305 -13.809 1.00 9.28 B c
ATOM 5823 CGI VAL H 349 -18.659 8.442 -12.626 1.00 9.24 B c
ATOM 5824 CG2 VAL H 349 -20.576 9.222 -14.033 1.00 9.94 B c
ATOM 5825 C VAL H 349 -17.126 10.861 -13.619 1.00 9.59 B c
ATOM 5826 O VAL H 349 -16.513 10.752 -14.681 1.00 9.69 B o
ATOM 5827 N SER H 350 -16.520 11.027 -12.449 1.00 9.93 B N
ATOM 5828 CA SER H 350 -15.073 11.104 -12.357 1.00 10.44 B c
ATOM 5829 CB SER H 350 -14.646 12.227 -11.408 1.00 10.04 B c
ATOM 5830 OG SER H 350 -14.584 13.468 -12.090 1.00 8.41 B o
ATOM 5831 C SER H 350 -14.459 9.773 -11.938 1.00 11.45 B c
ATOM 5832 O SER H 350 -15.000 9.062 -11.089 1.00 11.58 B o
ATOM 5833 N PHE H 351 -13.354 9.424 -12.587 1.00 12.28 B N
ATOM 5834 CA PHE H 351 -12.717 8.129 -12.403 1.00 13.04 B c
ATOM 5835 CB PHE H 351 -12.800 7.315 -13.697 1.00 12.87 B c
ATOM 5836 CG PHE H 351 -11.985 6.052 -13.677 1.00 13.52 B c
ATOM 5837 CD1 PHE H 351 -12.081 5.165 -12.615 1.00 13.76 B c
ATOM 5838 CE1 PHE H 351 -11.300 4.022 -12.574 1.00 14.10 B c
ATOM 5839 CZ PHE H 351 -10.453 3.726 -13.629 1.00 14.07 B c
ATOM 5840 CE2 PHE H 351 -10.381 4.583 -14.715 1.00 14.14 B c
ATOM 5841 CD2 PHE H 351 -11.134 5.744 -14.728 1.00 13.92 B c
ATOM 5842 C PHE H 351 -11.262 8.315 -11.993 1.00 13.84 B c
ATOM 5843 O PHE H 351 -10.528 9.090 -12.608 1.00 13.96 B o
ATOM 5844 N PHE H 352 -10.866 7.641 -10.919 1.00 14.72 B N
ATOM 5845 CA PHE H 352 -9.500 7.717 -10.418 1.00 15.98 B c
ATOM 5846 CB PHE H 352 -9.490 8.210 -8.966 1.00 15.75 B c
ATOM 5847 CG PHE H 352 -10.600 9.176 -8.638 1.00 15.51 B c
ATOM 5848 CD1 PHE H 352 -11.835 8.713 -8.210 1.00 15.05 B c
ATOM 5849 CE1 PHE H 352 -12.836 9.597 -7.837 1.00 14.05 B c
ATOM 5850 CZ PHE H 352 -12.592 10.955 -7.844 1.00 13.28 B c
ATOM 5851 CE2 PHE H 352 -11.343 11.426 -8.201 1.00 13.71 B c
ATOM 5852 CD2 PHE H 352 -10.347 10.536 -8.570 1.00 14.94 B c
ATOM 5853 C PHE H 352 -8.820 6.350 -10.511 1.00 17.56 B c
ATOM 5854 O PHE H 352 -9.259 5.390 -9.880 1.00 17.74 B O
ATOM 5855 N PRO H 353 -7.728 6.266 -11.288 1.00 19.05 B N
ATOM 5856 CA PRO H 353 -7.203 5.002 -11.802 1.00 20.40 B c
ATOM 5857 CB PRO H 353 -6.180 5.443 -12.859 1.00 20.26 B c
ATOM 5858 CG PRO H 353 -6.492 6.878 -13.145 1.00 19.71 B c
ATOM 5859 CD PRO H 353 -7.032 7.424 -11.869 1.00 18.97 B c
ATOM 5860 C PRO H 353 -6.522 4.135 -10.743 1.00 21.94 B c
ATOM 5861 O PRO H 353 -6.511 2.911 -10.873 1.00 22.29 B o ATOM 5862 N GLN H 354 -5.904 4.757 -9.742 1.00 23.38 B N
ATOM 5863 CA GLN H 354 -5.118 4.007 -8.760 1.00 24.64 B C
ATOM 5864 CB GLN H 354 -3.621 4.108 -9.064 1.00 24.93 B C
ATOM 5865 CG GLN H 354 -3.259 5.210 -10.038 1.00 26.00 B C
ATOM 5866 CD GLN H 354 -3.331 6.581 -9.407 1.00 25.92 B C
ATOM 5867 OE1 GLN H 354 -2.732 6.830 -8.360 1.00 25.67 B O
ATOM 5868 NE2 GLN H 354 -4.094 7.475 -10.025 1.00 24.27 B N
ATOM 5869 C GLN H 354 -5.393 4.393 -7.307 1.00 24.85 B C
ATOM 5870 O GLN H 354 -5.653 5.558 -7.007 1.00 24.51 B O
ATOM 5871 N ALA H 355 -5.162 3.446 -6.399 1.00 25.22 B N
ATOM 5872 CA ALA H 355 -5.563 3.599 -4.997 1.00 25.34 B C
ATOM 5873 CB ALA H 355 -5.112 2.400 -4.173 1.00 25.09 B C
ATOM 5874 C ALA H 355 -5.092 4.910 -4.354 1.00 24.92 B C
ATOM 5875 O ALA H 355 -5.901 5.647 -3.790 1.00 25.23 B O
ATOM 5876 N GLU H 356 -3.775 5.074 -4.242 1.00 23.93 B N
ATOM 5877 CA GLU H 356 -3.138 6.394 -4.141 1.00 22.77 B C
ATOM 5878 CB GLU H 356 -2.214 6.635 -5.339 1.00 23.22 B C
ATOM 5879 CG GLU H 356 -0.973 5.756 -5.344 1.00 26.33 B C
ATOM 5880 CD GLU H 356 -0.571 5.312 -3.948 1.00 30.93 B C
ATOM 5881 OE1 GLU H 356 -1.012 4.225 -3.516 1.00 31.97 B O
ATOM 5882 OE2 GLU H 356 0.074 6.111 -3.237 1.00 32.21 B O
ATOM 5883 C GLU H 356 -4.114 7.558 -3.990 1.00 21.31 B C
ATOM 5884 O GLU H 356 -4.098 8.270 -2.985 1.00 21.01 B O
ATOM 5885 N TH H 357 -4.868 7.819 -5.052 1.00 19.51 B N
ATOM 5886 CA THR H 357 -5.718 9.000 -5.138 1.00 17.55 B C
ATOM 5887 CB THR H 357 -6.391 9.086 -6.519 1.00 17.30 B C
ATOM 5888 OG1 THR H 357 -5.644 8.305 -7.462 1.00 17.32 B O
ATOM 5889 CG2 THR H 357 -6.472 10.531 -6.997 1.00 17.72 B C
ATOM 5890 C THR H 357 -6.801 9.006 -4.063 1.00 16.62 B C
ATOM 5891 O THR H 357 -7.346 10.058 -3.730 1.00 17.29 B O
ATOM 5892 N CYS H 358 -7.179 7.822 -3.594 1.00 14.88 B N
ATOM 5893 CA CYS H 358 -8.414 7.676 -2.833 1.00 13.15 B C
ATOM 5894 CB CYS H 358 -9.479 6.949 -3.655 1.00 13.04 B C
ATOM 5895 SG CYS H 358 -10.003 7.836 -5.144 1.00 14.02 B S
ATOM 5896 C CYS H 358 -8.202 6.982 -1.492 1.00 12.08 B C
ATOM 5897 O CYS H 358 -7.521 5.959 -1.408 1.00 12.15 B O
ATOM 5898 N LYS H 359 -8.741 7.585 -0.438 1.00 11.35 B N
ATOM 5899 CA LYS H 359 -8.861 6.922 0.853 1.00 11.01 B C
ATOM 5900 CB LYS H 359 -8.119 7.713 1.931 1.00 11.16 B C
ATOM 5901 CG LYS H 359 -7.413 8.953 1.414 1.00 13.28 B C
ATOM 5902 CD LYS H 359 -5.907 8.816 1.540 1.00 16.11 B C
ATOM 5903 CE LYS H 359 -5.199 10.088 1.104 1.00 17.91 B C
ATOM 5904 NZ LYS H 359 -3.719 9.952 1.184 1.00 20.99 B N
ATOM 5905 C LYS H 359 -10.325 6.777 1.242 1.00 10.46 B C
ATOM 5906 O LYS H 359 -11.191 7.462 0.697 1.00 10.70 B O
ATOM 5907 N VAL H 360 -10.579 5.977 2.270 1.00 9.99 B N
ATOM 5908 CA VAL H 360 -11.939 5.576 2.592 1.00 9.84 B C
ATOM 5909 CB VAL H 360 -12.406 4.401 1.712 1.00 9.42 B C
ATOM 5910 CGI VAL H 360 -11.411 3.253 1.784 1.00 10.07 B C
ATOM 5911 CG2 VAL H 360 -13.796 3.944 2.125 1.00 9.56 B C
ATOM 5912 C VAL H 360 -12.087 5.214 4.063 1.00 9.98 B C
ATOM 5913 O VAL H 360 -11.267 4.485 4.622 1.00 9.96 B O
ATOM 5914 N GLN H 361 -13.109 5.780 4.696 1.00 10.39 B N
ATOM 5915 CA GLN H 361 -13.322 5.606 6.125 1.00 11.53 B C
ATOM 5916 CB GLN H 361 -12.858 6.851 6.883 1.00 12.03 B C
ATOM 5917 CG GLN H 361 -13.051 6.769 8.385 1.00 16.44 B C
ATOM 5918 CD GLN H 361 -11.812 7.176 9.152 1.00 25.16 B C
ATOM 5919 OE1 GLN H 361 -11.763 8.257 9.738 1.00 29.01 B O
ATOM 5920 NE2 GLN H 361 -10.773 6.352 9.080 1.00 27.20 B N
ATOM 5921 C GLN H 361 -14.795 5.340 6.415 1.00 11.15 B C ATOM 5922 O GLN H 361 -15.620 6.253 6.355 1.00 11.80 B O
ATOM 5923 N SER H 362 -15.136 4.078 6.650 1.00 10.90 B N
ATOM 5924 CA SER H 362 -16.529 3.677 6.634 1.00 10.30 B C
ATOM 5925 CB SER H 362 -17.326 4.548 7.603 1.00 10.47 B C
ATOM 5926 OG SER H 362 -18.616 4.011 7.823 1.00 11.17 B O
ATOM 5927 C SER H 362 -17.074 3.846 5.224 1.00 9.58 B C
ATOM 5928 O SER H 362 -16.419 3.474 4.250 1.00 9.48 B O
ATOM 5929 N ASN H 363 -18.182 4.569 5.115 1.00 9.12 B N
ATOM 5930 CA ASN H 363 -18.810 4.826 3.826 1.00 8.73 B C
ATOM 5931 CB ASN H 363 -20.329 4.778 3.972 1.00 9.01 B C
ATOM 5932 CG ASN H 363 -20.850 5.801 4.965 1.00 9.29 B C
ATOM 5933 OD1 ASN H 363 -20.079 6.555 5.561 1.00 9.82 B O
ATOM 5934 ND2 ASN H 363 -22.162 5.818 5.163 1.00 10.08 B N
ATOM 5935 C ASN H 363 -18.382 6.185 3.277 1.00 8.12 B C
ATOM 5936 O ASN H 363 -18.996 6.720 2.352 1.00 8.10 B O
ATOM 5937 N ARG H 364 -17.346 6.749 3.890 1.00 7.20 B N
ATOM 5938 CA ARG H 364 -16.777 8.017 3.457 1.00 6.82 B C
ATOM 5939 CB ARG H 364 -16.307 8.821 4.671 1.00 6.91 B C
ATOM 5940 CG ARG H 364 -16.741 10.271 4.655 1.00 7.92 B C
ATOM 5941 CD ARG H 364 -18.197 10.397 4.249 1.00 8.20 B C
ATOM 5942 NE ARG H 364 -18.377 11.314 3.127 1.00 8.70 B N
ATOM 5943 CZ ARG H 364 -19.450 12.077 2.958 1.00 8.88 B C
ATOM 5944 NHl ARG H 364 -20.420 12.062 3.862 1.00 8.57 B N
ATOM 5945 NH2 ARG H 364 -19.546 12.867 1.897 1.00 10.59 B N
ATOM 5946 C ARG H 364 -15.603 7.775 2.519 1.00 6.58 B C
ATOM 5947 O ARG H 364 -14.680 7.030 2.847 1.00 6.65 B O
ATOM 5948 N VAL H 365 -15.619 8.448 1.375 1.00 6.64 B N
ATOM 5949 CA VAL H 365 -14.526 8.350 0.419 1.00 6.54 B C
ATOM 5950 CB VAL H 365 -15.000 7.763 -0.922 1.00 5.95 B C
ATOM 5951 CGI VAL H 365 -13.934 7.950 -1.990 1.00 5.48 B C
ATOM 5952 CG2 VAL H 365 -15.350 6.292 -0.762 1.00 6.22 B C
ATOM 5953 C VAL H 365 -13.914 9.719 0.166 1.00 7.35 B C
ATOM 5954 O VAL H 365 -14.617 10.729 0.128 1.00 8.33 B O
ATOM 5955 N PHE H 366 -12.611 9.733 -0.081 1.00 7.37 B N
ATOM 5956 CA PHE H 366 -11.904 10.969 -0.360 1.00 7.44 B C
ATOM 5957 CB PHE H 366 -11.137 11.431 0.874 1.00 7.30 B C
ATOM 5958 CG PHE H 366 -12.009 11.714 2.054 1.00 6.70 B C
ATOM 5959 CD1 PHE H 366 -12.571 10.677 2.778 1.00 6.70 B C
ATOM 5960 CE1 PHE H 366 -13.347 10.932 3.894 1.00 5.94 B C
ATOM 5961 CZ PHE H 366 -13.546 12.236 4.311 1.00 5.71 B C
ATOM 5962 CE2 PHE H 366 -12.990 13.279 3.593 1.00 5.96 B C
ATOM 5963 CD2 PHE H 366 -12.235 13.015 2.467 1.00 6.52 B C
ATOM 5964 C PHE H 366 -10.939 10.777 -1.511 1.00 7.45 B C
ATOM 5965 O PHE H 366 -9.931 10.082 -1.381 1.00 7.45 B O
ATOM 5966 N CYS H 367 -11.212 11.453 -2.618 1.00 8.00 B N
ATOM 5967 CA CYS H 367 -10.408 11.281 -3.809 1.00 8.90 B C
ATOM 5968 CB CYS H 367 -11.217 10.596 -4.909 1.00 9.46 B C
ATOM 5969 SG CYS H 367 -11.640 8.877 -4.545 1.00 10.79 B S
ATOM 5970 C CYS H 367 -9.870 12.612 -4.297 1.00 9.09 B C
ATOM 5971 O CYS H 367 -10.363 13.674 -3.919 1.00 9.24 B O
ATOM 5972 N ASP H 368 -8.892 12.540 -5.188 1.00 9.54 B N
ATOM 5973 CA ASP H 368 -8.190 13.724 -5.637 1.00 10.55 B C
ATOM 5974 CB ASP H 368 -6.693 13.584 -5.372 1.00 10.53 B C
ATOM 5975 CG ASP H 368 -5.983 14.917 -5.352 1.00 11.11 B C
ATOM 5976 OD1 ASP H 368 -6.335 15.787 -6.177 1.00 11.42 B O
ATOM 5977 OD2 ASP H 368 -5.158 15.138 -4.441 1.00 11.35 B O
ATOM 5978 C ASP H 368 -8.442 13.949 -7.118 1.00 11.45 B C
ATOM 5979 O ASP H 368 -8.036 13.143 -7.955 1.00 12.05 B O
ATOM 5980 N THR H 369 -9.222 14.980 -7.425 1.00 12.41 B N
ATOM 5981 CA THR H 369 -9.359 15.444 -8.796 1.00 13.00 B C ATOM 5982 CB TH H 369 -9.723 16.934 -8.846 1.00 12.69 B C
ATOM 5983 OG1 THR H 369 -10.937 17.158 -8.117 1.00 11.72 B o
ATOM 5984 CG2 THR H 369 -9.896 17.390 -10.289 1.00 13.33 B c
ATOM 5985 C THR H 369 -8.052 15.254■ -9.548 1.00 14.13 B c
ATOM 5986 O THR H 369 -7.986 14.504 - 10.520 1.00 14.72 B o
ATOM 5987 N MET H 370 -6.996 15.868 -9.029 1.00 15.25 B N
ATOM 5988 CA MET H 370 -5.822 16.195 -9.825 1.00 16.60 B c
ATOM 5989 CB MET H 370 -4.542 15.983 -9.019 1.00 17.42 B c
ATOM 5990 CG MET H 370 -3.815 17.270 -8.673 1.00 20.31 B c
ATOM 5991 SD MET H 370 -3.256 18.144 -10.144 1.00 26.43 B s
ATOM 5992 CE MET H 370 -4.817 18.449 -10.970 1.00 24.07 B c
ATOM 5993 C MET H 370 -5.752 15.466 - 11.165 1.00 16.54 B c
ATOM 5994 O MET H 370 -5.659 16.108 - 12.209 1.00 16.74 B o
ATOM 5995 N ASN H 371 -5.730 14.137 - 11.146 1.00 16.35 B N
ATOM 5996 CA ASN H 371 -5.564 13.390 -12.394 1.00 16.07 B c
ATOM 5997 CB ASN H 371 -4.271 12.573 -12.386 1.00 16.41 B c
ATOM 5998 CG ASN H 371 -3.047 13.428 -12.644 1.00 16.71 B c
ATOM 5999 OD1 ASN H 371 -2.747 13.766 -13.790 1.00 15.75 B O
ATOM 6000 ND2 ASN H 371 -2.401 13.874 -11.572 1.00 17.76 B N
ATOM 6001 C ASN H 371 -6.767 12.552 -12.827 1.00 15.55 B C
ATOM 6002 O ASN H 371 -6.757 11.959 -13.907 1.00 15.84 B O
ATOM 6003 N SER H 372 -7.879 12.750 -12.126 1.00 14.76 B N
ATOM 6004 CA SER H 372 -9.165 12.189 -12.526 1.00 13.91 B C
ATOM 6005 CB SER H 372 -10.309 12.932 -11.832 1.00 14.04 B C
ATOM 6006 OG SER H 372 -10.226 14.328 -12.061 1.00 15.09 B O
ATOM 6007 C SER H 372 -9.372 12.202 -14.037 1.00 13.07 B C
ATOM 6008 O SER H 372 -8.839 13.056 -14.743 1.00 13.02 B O
ATOM 6009 N LEU H 373 -10.112 11.213 -14.526 1.00 12.23 B N
ATOM 6010 CA LEU H 373 -10.687 11.256 -15.864 1.00 11.45 B C
ATOM 6011 CB LEU H 373 -10.417 9.939 -16.594 1.00 11.43 B C
ATOM 6012 CG LEU H 373 -9.204 9.880 -17.524 1.00 11.04 B C
ATOM 6013 CD1 LEU H 373 -7.988 10.551 -16.888 1.00 11.76 B C
ATOM 6014 CD2 LEU H 373 -8.894 8.435 -17.915 1.00 10.49 B C
ATOM 6015 C LEU H 373 -12.188 11.472 -15.762 1.00 11.17 B C
ATOM 6016 O LEU H 373 -12.847 10.886 -14.904 1.00 11.27 B O
ATOM 6017 N THR H 374 -12.733 12.289 -16.655 1.00 10.70 B N
ATOM 6018 CA THR H 374 -14.144 12.637 -16.586 1.00 10.23 B C
ATOM 6019 CB THR H 374 -14.367 14.151 -16.730 1.00 10.24 B C
ATOM 6020 OG1 THR H 374 -13.177 14.850 -16.344 1.00 11.25 B O
ATOM 6021 CG2 THR H 374 -15.521 14.604 -15.849 1.00 10.52 B C
ATOM 6022 C THR H 374 -14.953 11.896 -17.641 1.00 9.54 B C
ATOM 6023 O THR H 374 -14.580 11.855 -18.813 1.00 9.70 B o
ATOM 6024 N LEU H 375 -16.035 11.266 -17.198 1.00 8.83 B N
ATOM 6025 CA LEU H 375 -16.731 10.270 -18.000 1.00 7.83 B C
ATOM 6026 CB LEU H 375 -16.360 8.861 -17.540 1.00 7.38 B c
ATOM 6027 CG LEU H 375 -14.878 8.495 -17.551 1.00 5.06 B c
ATOM 6028 CD1 LEU H 375 -14.710 7.045 -17.124 1.00 2.41 B c
ATOM 6029 CD2 LEU H 375 -14.288 8.729 -18.934 1.00 4.31 B c
ATOM 6030 C LEU H 375 -18.236 10.456 -17.878 1.00 7.79 B c
ATOM 6031 O LEU H 375 -18.724 10.928 -16.850 1.00 7.92 B o
ATOM 6032 N PRO H 376 -18.982 9.954 -18.871 1.00 7.51 B N
ATOM 6033 CA PRO H 376 -20.439 10.009 -18.882 1.00 7.90 B c
ATOM 6034 CB PRO H 376 -20.780 9.837 -20.362 1.00 7.90 B c
ATOM 6035 CG PRO H 376 -19.657 9.033 -20.908 1.00 7.97 B c
ATOM 6036 CD PRO H 376 -18.435 9.468 -20.150 1.00 7.40 B c
ATOM 6037 C PRO H 376 -21.063 8.881 -18.064 1.00 8.35 B c
ATOM 6038 O PRO H 376 -20.569 7.753 -18.085 1.00 8.71 B o
ATOM 6039 N SER H 377 -22.190 9.172 -17.421 1.00 9.11 B N
ATOM 6040 CA SER H 377 -22.937 8.165 -16.673 1.00 9.91 B c
ATOM 6041 CB SER H 377 -24.272 8.737 -16.191 1.00 10.23 B c ATOM 6042 OG SE H 377 -24.293 10.150 -16.304 1.00 10.90 B O
ATOM 6043 C SER H 377 -23.180 1 5.915 -17.513 1.00 10.14 B C
ATOM 6044 O SER H 377 -23.678 5.906 -17.013 1.00 10.08 B O
ATOM 6045 N GLU H 378 -22.875 7.010 -18.803 1.00 10.71 B N
ATOM 6046 CA GLU H 378 -23.057 5.893 -19.721 1.00 11.40 B C
ATOM 6047 CB GLU H 378 -22.970 6.377 -21.170 1.00 11.65 B C
ATOM 6048 CG GLU H 378 -24.261 6.977 -21.706 1.00 13.46 B c
ATOM 6049 CD GLU H 378 -24.671 8.241 -20.972 1.00 16.20 B c
ATOM 6050 OE1 GLU H 378 -23.922 8.681 -20.074 1.00 15.73 B o
ATOM 6051 OE2 GLU H 378 -25.749 8.788 -21.285 1.00 18.38 B o
ATOM 6052 C GLU H 378 -22.019 4.805 -19.468 1.00 11.27 B c
ATOM 6053 O GLU H 378 -22.196 3.657 -19.877 1.00 11.28 B o
ATOM 6054 N VAL H 379 -20.943 5.170 -18.779 1.00 11.31 B N
ATOM 6055 CA VAL H 379 -19.977 4.192 -18.296 1.00 11.59 B c
ATOM 6056 CB VAL H 379 -18.973 4.824 -17.315 1.00 11.27 B c
ATOM 6057 CGI VAL H 379 -18.343 3.752 -16.440 1.00 11.60 B c
ATOM 6058 CG2 VAL H 379 -17.905 5.597 -18.073 1.00 11.54 B c
ATOM 6059 C VAL H 379 -20.675 3.023 -17.610 1.00 12.16 B c
ATOM 6060 O VAL H 379 -20.260 1.872 -17.750 1.00 12.51 B o
ATOM 6061 N ASN H 380 -21.769 3.317 -16.915 1.00 12.98 B N
ATOM 6062 CA ASN H 380 -22.428 2.328 -16.068 1.00 14.00 B c
ATOM 6063 CB ASN H 380 -23.553 2.973 -15.258 1.00 14.59 B c
ATOM 6064 CG ASN H 380 -23.038 3.964 -14.234 1.00 17.09 B c
ATOM 6065 OD1 ASN H 380 -22.893 3.637 -13.056 1.00 20.41 B o
ATOM 6066 ND2 ASN H 380 -22.690 5.160 -14.693 1.00 18.86 B N
ATOM 6067 C ASN H 380 -22.954 1.115 -16.833 1.00 13.96 B c
ATOM 6068 O ASN H 380 -22.973 0.005 -16.302 1.00 14.38 B o
ATOM 6069 N LEU H 381 -23.459 1.343 -18.042 1.00 13.61 B N
ATOM 6070 CA LEU H 381 -24.024 0.261 -18.844 1.00 13.72 B c
ATOM 6071 CB LEU H 381 -24.514 0.792 -20.191 1.00 13.79 B c
ATOM 6072 CG LEU H 381 -25.004 2.240 -20.194 1.00 14.92 B c
ATOM 6073 CD1 LEU H 381 -25.409 2.670 -21.595 1.00 15.56 B c
ATOM 6074 CD2 LEU H 381 -26.157 2.422 -19.218 1.00 15.78 B c
ATOM 6075 C LEU H 381 -22.982 - 0.827 -19.060 1.00 13.62 B c
ATOM 6076 O LEU H 381 -23.314 - ■1.973 -19.365 1.00 13.57 B o
ATOM 6077 N CYS H 382 -21.729 - ■0.478 -18.796 1.00 13.47 B N
ATOM 6078 CA CYS H 382 -20.615 -1.367 -19.068 1.00 13.57 B c
ATOM 6079 CB CYS H 382 -19.321 -0.565 -19.165 1.00 13.62 B c
ATOM 6080 SG CYS H 382 -18.814 -0.217 -20.852 1.00 15.64 B s
ATOM 6081 C CYS H 382 -20.494 - 2.432 -17.987 1.00 13.33 B c
ATOM 6082 O CYS H 382 -19.948 - ■3.510 -18.224 1.00 13.57 B o
ATOM 6083 N ASN H 383 -21.096■ -2.163 -16.833 1.00 13.21 B N
ATOM 6084 CA ASN H 383 -21.267 -3.181 -15.803 1.00 13.22 B c
ATOM 6085 CB ASN H 383 -21.854 -2.568 -14.531 1.00 13.18 B c
ATOM 6086 CG ASN H 383 -21.059 -1.381 -14.034 1.00 13.42 B c
ATOM 6087 OD1 ASN H 383 -19.830 -1.418 -13.985 1.00 13.68 B o
ATOM 6088 ND2 ASN H 383 -21.761 -0.330 -13.626 1.00 14.32 B N
ATOM 6089 C ASN H 383 -22.159 - ■4.317 -16.277 1.00 13.28 B c
ATOM 6090 O ASN H 383 -22.096■ -5.428 -15.751 1.00 13.50 B o
ATOM 6091 N VAL H 384 -23.092 -3.990 -17.164 1.00 13.24 B N
ATOM 6092 CA VAL H 384 -24.065 -4.964 -17.630 1.00 13.29 B c
ATOM 6093 CB VAL H 384 -25.484 -4.367 -17.709 1.00 13.28 B c
ATOM 6094 CGI VAL H 384 -26.371 -5.222 -18.601 1.00 13.73 B c
ATOM 6095 CG2 VAL H 384 -26.083 -4.241 -16.315 1.00 12.76 B c
ATOM 6096 C VAL H 384 -23.677 ■ -5.563 -18.977 1.00 13.57 B c
ATOM 6097 O VAL H 384 -23.940 -6.737 -19.233 1.00 13.31 B o
ATOM 6098 N ASP H 385 -23.060 - 4.764 -19.843 1.00 14.07 B N
ATOM 6099 CA ASP H 385 -22.923 -5.172 -21.238 1.00 14.61 B c
ATOM 6100 CB ASP H 385 -23.915 -4.459 -22.154 1.00 14.71 B c
ATOM 6101 CG ASP H 385 -24.584 -5.410 -23.130 1.00 16.69 B c ATOM 6102 OD1 ASP H 385 -24.093 -6.549 -23.281 1.00 18.63 B O
ATOM 6103 OD2 ASP H 385 -25.614 -5.030 -23.724 1.00 19.10 B O
ATOM 6104 C ASP H 385 -21.525 -5.244 -21.851 1.00 14.63 B C
ATOM 6105 O ASP H 385 -21.203 -6.221 -22.526 1.00 14.34 B O
ATOM 6106 N ILE H 386 -20.722 -4.198 -21.691 1.00 14.54 B N
ATOM 6107 CA ILE H 386 -19.435 -4.146 -22.382 1.00 14.46 B C
ATOM 6108 CB ILE H 386 -18.772 -5.540 -22.417 1.00 13.83 B C
ATOM 6109 CGI ILE H 386 -18.450 -6.032 -21.009 1.00 13.44 B C
ATOM 6110 CD1 ILE H 386 -18.701 -7.516 -20.821 1.00 12.39 B C
ATOM 6111 CG2 ILE H 386 -17.533 -5.525 -23.298 1.00 13.51 B C
ATOM 6112 C ILE H 386 -19.673 -3.755 -23.830 1.00 14.73 B C
ATOM 6113 O ILE H 386 -19.266 -2.682 -24.274 1.00 14.68 B O
ATOM 6114 N PHE H 387 -20.135 -4.733 -24.601 1.00 14.71 B N
ATOM 6115 CA PHE H 387 -20.696 -4.482 -25.915 1.00 14.78 B C
ATOM 6116 CB PHE H 387 -20.739 -5.766 -26.733 1.00 14.77 B C
ATOM 6117 CG PHE H 387 -19.482 -6.569 -26.647 1.00 14.75 B C
ATOM 6118 CD1 PHE H 387 -19.407 -7.658 -25.797 1.00 15.03 B C
ATOM 6119 CE1 PHE H 387 -18.229 -8.368 -25.662 1.00 14.62 B C
ATOM 6120 CZ PHE H 387 -17.093 -7.943 -26.318 1.00 14.55 B C
ATOM 6121 CE2 PHE H 387 -17.136 -6.809 -27.103 1.00 14.68 B C
ATOM 6122 CD2 PHE H 387 -18.316 -6.103 -27.227 1.00 14.61 B C
ATOM 6123 C PHE H 387 -22.080 -3.871 -25.821 1.00 14.91 B C
ATOM 6124 O PHE H 387 -22.992 -4.445 -25.228 1.00 14.86 B O
ATOM 6125 N ASN H 388 -22.144 -2.610 -26.216 1.00 15.11 B N
ATOM 6126 CA ASN H 388 -23.383 -1.869 -26.295 1.00 15.38 B C
ATOM 6127 CB ASN H 388 -23.968 -1.663 -24.897 1.00 14.86 B C
ATOM 6128 CG ASN H 388 -23.005 -0.958 -23.963 1.00 14.86 B C
ATOM 6129 OD1 ASN H 388 -22.936 0.270 -23.935 1.00 12.80 B O
ATOM 6130 ND2 ASN H 388 -22.213 -1.736 -23.234 1.00 15.97 B N
ATOM 6131 C ASN H 388 -23.023 -0.526 -26.906 1.00 16.11 B C
ATOM 6132 O ASN H 388 -21.965 0.024 -26.599 1.00 15.92 B O
ATOM 6133 N PRO H 389 -23.772 -0.117 -27.935 1.00 16.99 B N
ATOM 6134 CA PRO H 389 -23.716 1.289 -28.309 1.00 17.40 B C
ATOM 6135 CB PRO H 389 -24.965 1.468 -29.176 1.00 17.72 B C
ATOM 6136 CG PRO H 389 -25.904 0.425 -28.694 1.00 17.47 B C
ATOM 6137 CD PRO H 389 -25.041 -0.747 -28.339 1.00 17.05 B C
ATOM 6138 C PRO H 389 -23.810 2.170 -27.071 1.00 17.86 B C
ATOM 6139 O PRO H 389 -24.276 1.718 -26.025 1.00 18.45 B O
ATOM 6140 N LYS H 390 -23.335 3.406 -27.180 1.00 17.97 B N
ATOM 6141 CA LYS H 390 -23.325 4.318 -26.045 1.00 18.06 B C
ATOM 6142 CB LYS H 390 -24.373 3.904 -25.009 1.00 17.92 B C
ATOM 6143 CG LYS H 390 -25.807 4.197 -25.424 1.00 18.58 B C
ATOM 6144 CD LYS H 390 -26.259 5.564 -24.935 1.00 20.61 B C
ATOM 6145 CE LYS H 390 -27.775 5.656 -24.875 1.00 21.48 B C
ATOM 6146 NZ LYS H 390 -28.387 5.669 -26.232 1.00 23.16 B N
ATOM 6147 C LYS H 390 -21.946 4.403 -25.400 1.00 18.01 B C
ATOM 6148 O LYS H 390 -21.382 5.490 -25.279 1.00 18.43 B O
ATOM 6149 N TYR H 391 -21.391 3.261 -25.011 1.00 17.68 B N
ATOM 6150 CA TYR H 391 -20.012 3.232 -24.539 1.00 17.33 B C
ATOM 6151 CB TYR H 391 -19.948 3.140 -23.015 1.00 17.42 B C
ATOM 6152 CG TYR H 391 -18.847 3.986 -22.423 1.00 17.27 B C
ATOM 6153 CD1 TYR H 391 -18.602 5.263 -22.911 1.00 17.29 B C
ATOM 6154 CE1 TYR H 391 -17.553 6.021 -22.434 1.00 17.32 B C
ATOM 6155 CZ TYR H 391 -16.698 5.486 -21.496 1.00 16.51 B C
ATOM 6156 OH TYR H 391 -15.654 6.241 -21.015 1.00 16.65 B O
ATOM 6157 CE2 TYR H 391 -16.878 4.195 -21.045 1.00 16.52 B C
ATOM 6158 CD2 TYR H 391 -17.933 3.444 -21.530 1.00 17.24 B C
ATOM 6159 C TYR H 391 -19.179 2.130 -25.176 1.00 17.43 B C
ATOM 6160 O TYR H 391 -19.459 0.946 -24.993 1.00 17.70 B O
ATOM 6161 N ASP H 392 -18.075 2.522 -25.804 1.00 17.56 B N ATOM 6162 CA ASP H 392 -16.973 1.599 -26.012 1.00 17.69 B C
ATOM 6163 CB ASP H 392 -16.119 2.003 -27.214 1.00 17.89 B C
ATOM 6164 CG ASP H 392 -16.587 3.290 -27.853 1.00 18.86 B C
ATOM 6165 OD1 ASP H 392 -16.582 4.332 -27.165 1.00 20.34 B O
ATOM 6166 OD2 ASP H 392 -16.931 3.269 -29.053 1.00 18.51 B O
ATOM 6167 C ASP H 392 -16.115 1.473 -24.767 1.00 17.11 B C
ATOM 6168 O ASP H 392 -15.801 2.460 -24.101 1.00 17.04 B O
ATOM 6169 N CYS H 393 -15.736 0.239 -24.468 1.00 16.33 B N
ATOM 6170 CA CYS H 393 -15.683 -0.240 -23.102 1.00 16.17 B C
ATOM 6171 CB CYS H 393 -16.818 -1.230 -22.851 1.00 16.11 B C
ATOM 6172 SG CYS H 393 -17.226 -1.449 -21.117 1.00 20.23 B S
ATOM 6173 C CYS H 393 -14.355 -0.941 -22.926 1.00 15.37 B C
ATOM 6174 O CYS H 393 -14.044 -1.876 -23.663 1.00 15.15 B O
ATOM 6175 N LYS H 394 -13.482 -0.332 -22.138 1.00 14.91 B N
ATOM 6176 CA LYS H 394 -12.100 -0.755 -22.107 1.00 14.50 B C
ATOM 6177 CB LYS H 394 -11.242 0.294 -21.405 1.00 14.60 B C
ATOM 6178 CG LYS H 394 -11.613 1.723 -21.788 1.00 16.44 B C
ATOM 6179 CD LYS H 394 -10.460 2.688 -21.576 1.00 20.45 B C
ATOM 6180 CE LYS H 394 -10.252 2.974 -20.099 1.00 23.05 B C
ATOM 6181 NZ LYS H 394 -9.330 1.988 -19.467 1.00 24.13 B N
ATOM 6182 C LYS H 394 -11.955 -2.130 -21.463 1.00 14.00 B C
ATOM 6183 O LYS H 394 -12.593 -2.434 -20.454 1.00 14.14 B O
ATOM 6184 N ILE H 395 -11.118 -2.957 -22.077 1.00 13.28 B N
ATOM 6185 CA ILE H 395 -11.238 -4.407 -22.026 1.00 12.89 B C
ATOM 6186 CB ILE H 395 -12.208 -4.925 -23.106 1.00 12.75 B C
ATOM 6187 CGI ILE H 395 -13.660 -4.699 -22.690 1.00 13.58 B C
ATOM 6188 CD1 ILE H 395 -14.633 -4.719 -23.849 1.00 15.33 B C
ATOM 6189 CG2 ILE H 395 -11.947 -6.396 -23.399 1.00 12.16 B C
ATOM 6190 C ILE H 395 -9.860 -4.906 -22.407 1.00 13.15 B C
ATOM 6191 O ILE H 395 -9.242 -4.353 -23.312 1.00 13.45 B O
ATOM 6192 N MET H 396 -9.462 -6.054 -21.877 1.00 13.06 B N
ATOM 6193 CA MET H 396 -8.356 -6.773 -22.482 1.00 13.00 B C
ATOM 6194 CB MET H 396 -7.104 -6.717 -21.605 1.00 13.34 B C
ATOM 6195 CG MET H 396 -7.052 -7.752 -20.500 1.00 14.30 B C
ATOM 6196 SD MET H 396 -5.571 -7.581 -19.484 1.00 18.50 B S
ATOM 6197 CE MET H 396 -5.752 -5.895 -18.904 1.00 17.80 B C
ATOM 6198 C MET H 396 -8.702 -8.200 -22.867 1.00 12.96 B C
ATOM 6199 O MET H 396 -9.615 -8.808 -22.309 1.00 13.04 B O
ATOM 6200 N TH H 397 -7.935 -8.734 -23.808 1.00 12.78 B N
ATOM 6201 CA THR H 397 -8.350 -9.888 -24.585 1.00 12.51 B C
ATOM 6202 CB THR H 397 -8.389 -9.563 -26.087 1.00 12.39 B C
ATOM 6203 OG1 THR H 397 -9.593 -8.851 -26.394 1.00 12.50 B O
ATOM 6204 CG2 THR H 397 -8.335 -10.839 -26.912 1.00 12.55 B C
ATOM 6205 C THR H 397 -7.350 -11.005 -24.366 1.00 12.58 B C
ATOM 6206 O THR H 397 -6.143 -10.772 -24.327 1.00 12.88 B O
ATOM 6207 N SER H 398 -7.859 -12.210 -24.165 1.00 12.55 B N
ATOM 6208 CA SER H 398 -7.082 -13.401 -24.410 1.00 12.76 B C
ATOM 6209 CB SER H 398 -6.083 -13.627 -23.273 1.00 12.52 B C
ATOM 6210 OG SER H 398 -5.764 -15.001 -23.133 1.00 12.72 B O
ATOM 6211 C SER H 398 -8.070 -14.539 -24.456 1.00 12.99 B C
ATOM 6212 O SER H 398 -8.838 -14.672 -25.410 1.00 13.13 B O
ATOM 6213 N LYS H 399 -8.182 -15.232 -23.330 1.00 13.01 B N
ATOM 6214 CA LYS H 399 -7.890 -16.651 -23.342 1.00 13.29 B C
ATOM 6215 CB LYS H 399 -6.739 -17.020 -24.279 1.00 13.79 B C
ATOM 6216 CG LYS H 399 -6.786 -16.279 -25.618 1.00 14.34 B C
ATOM 6217 CD LYS H 399 -7.835 -16.868 -26.552 1.00 16.43 B C
ATOM 6218 CE LYS H 399 -7.864 -16.139 -27.889 1.00 17.37 B C
ATOM 6219 NZ LYS H 399 -8.770 -16.802 -28.867 1.00 16.62 B N
ATOM 6220 C LYS H 399 -8.128 -17.609 -22.171 1.00 13.09 B C
ATOM 6221 O LYS H 399 -9.087 -18.376 -22.216 1.00 12.87 B O ATOM 6222 N TH H 400 -7.140 -17.783 -21.300 1.00 13.04 B N
ATOM 6223 CA THR H 400 -7.133 -18.953 -20.420 1.00 13.38 B C
ATOM 6224 CB THR H 400 -5.703 -19.453 -20.133 1.00 13.74 B C
ATOM 6225 OG1 THR H 400 -4.773 -18.763 -20.977 1.00 14.38 B O
ATOM 6226 CG2 THR H 400 -5.601 -20.950 -20.394 1.00 14.32 B C
ATOM 6227 C THR H 400 -7.866 -18.687 -19.104 1.00 13.20 B C
ATOM 6228 O THR H 400 -7.913 -17.551 -18.630 1.00 13.12 B O
ATOM 6229 N ASP H 401 -8.478 -19.728 -18.545 1.00 12.97 B N
ATOM 6230 CA ASP H 401 -8.896 -19.715 -17.145 1.00 12.50 B C
ATOM 6231 CB ASP H 401 -9.622 -21.022 -16.798 1.00 12.73 B C
ATOM 6232 CG ASP H 401 -10.854 -21.261 -17.651 1.00 13.98 B C
ATOM 6233 OD1 ASP H 401 -10.870 -20.793 -18.808 1.00 16.55 B O
ATOM 6234 OD2 ASP H 401 -11.708 -22.076 -17.236 1.00 14.80 B O
ATOM 6235 C ASP H 401 -7.683 -19.567 -16.222 1.00 12.13 B C
ATOM 6236 O ASP H 401 -6.906 -20.508 -16.071 1.00 12.31 B O
ATOM 6237 N VAL H 402 -7.609 -18.459 -15.489 1.00 11.49 B N
ATOM 6238 CA VAL H 402 -7.400 -18.523 -14.044 1.00 10.74 B C
ATOM 6239 CB VAL H 402 -7.004 -17.151 -13.456 1.00 10.60 B C
ATOM 6240 CGI VAL H 402 -7.433 -17.045 -11.998 1.00 11.26 B C
ATOM 6241 CG2 VAL H 402 -5.504 -16.918 -13.602 1.00 10.99 B C
ATOM 6242 C VAL H 402 -8.707 -18.986 -13.423 1.00 10.24 B C
ATOM 6243 O VAL H 402 -9.515 -19.616 -14.104 1.00 10.30 B O
ATOM 6244 N SER H 403 -9.015 -18.516 -12.218 1.00 9.76 B N
ATOM 6245 CA SER H 403 -10.286 -18.897 -11.605 1.00 9.18 B C
ATOM 6246 CB SER H 403 -10.485 -20.406 -11.726 1.00 9.41 B C
ATOM 6247 OG SER H 403 -9.349 -21.015 -12.313 1.00 10.82 B O
ATOM 6248 C SER H 403 -10.528 -18.449 -10.162 1.00 8.51 B C
ATOM 6249 O SER H 403 -9.701 -18.699 -9.285 1.00 8.30 B O
ATOM 6250 N SER H 404 -11.773 -18.053 -9.888 1.00 8.35 B N
ATOM 6251 CA SER H 404 -12.352 -18.148 -8.541 1.00 8.18 B C
ATOM 6252 CB SER H 404 -11.585 -17.257 -7.564 1.00 8.18 B C
ATOM 6253 OG SER H 404 -12.250 -16.019 -7.382 1.00 8.83 B O
ATOM 6254 C SER H 404 -13.841 -17.789 -8.505 1.00 7.62 B C
ATOM 6255 O SER H 404 -14.505 -17.759 -9.541 1.00 7.57 B O
ATOM 6256 N SER H 405 -14.357 -17.506 -7.310 1.00 7.08 B N
ATOM 6257 CA SER H 405 -15.777 -17.210 -7.151 1.00 6.53 B C
ATOM 6258 CB SER H 405 -16.568 -18.475 -6.802 1.00 6.42 B C
ATOM 6259 OG SER H 405 -17.786 -18.156 -6.146 1.00 5.66 B O
ATOM 6260 C SER H 405 -16.070 -16.101 -6.144 1.00 6.28 B C
ATOM 6261 O SER H 405 -15.289 -15.847 -5.226 1.00 5.98 B O
ATOM 6262 N VAL H 406 -17.254 -15.514 -6.281 1.00 6.22 B N
ATOM 6263 CA VAL H 406 -17.629 -14.309 -5.557 1.00 6.50 B C
ATOM 6264 CB VAL H 406 -17.390 -13.053 -6.414 1.00 6.45 B C
ATOM 6265 CGI VAL H 406 -17.384 -11.811 -5.546 1.00 7.66 B C
ATOM 6266 CG2 VAL H 406 -16.090 -13.177 -7.191 1.00 7.38 B C
ATOM 6267 C VAL H 406 -19.115 -14.377 -5.237 1.00 6.24 B C
ATOM 6268 O VAL H 406 -19.946 -14.488 -6.138 1.00 6.14 B O
ATOM 6269 N ILE H 407 -19.450 -14.313 -3.955 1.00 6.32 B N
ATOM 6270 CA ILE H 407 -20.831 -14.478 -3.534 1.00 6.60 B C
ATOM 6271 CB ILE H 407 -20.925 -15.154 -2.163 1.00 6.27 B C
ATOM 6272 CGI ILE H 407 -20.643 -16.651 -2.296 1.00 6.19 B C
ATOM 6273 CD 1 ILE H 407 -21.477 -17.514 -1.376 1.00 8.34 B C
ATOM 6274 CG2 ILE H 407 -22.294 -14.923 -1.550 1.00 6.42 B C
ATOM 6275 C ILE H 407 -21.570 -13.149 -3.497 1.00 7.20 B C
ATOM 6276 O ILE H 407 -21.094 -12.176 -2.913 1.00 7.42 B O
ATOM 6277 N THR H 408 -22.792 -13.155 -4.016 1.00 7.57 B N
ATOM 6278 CA THR H 408 -23.563 -11.933 -4.148 1.00 8.19 B C
ATOM 6279 CB THR H 408 -24.066 -11.739 -5.587 1.00 8.15 B C
ATOM 6280 OG1 THR H 408 -24.863 -12.866 -5.971 1.00 8.88 B O
ATOM 6281 CG2 THR H 408 -22.893 -11.606 -6.542 1.00 7.93 B C ATOM 6282 C TH H408 -24.753 -11.933 -3.203 1.00 8.55 B C
ATOM 6283 O THRH408 -24.998 -12.905 -2.488 1.009.07 B o
ATOM 6284 N SERH409 -25.513 -10.844 -3.238 1.008.70 B N
ATOM 6285 CA SE H409 -26.644-10.667 -2.344 1.009.20 B C
ATOM 6286 CB SERH409 -27.266 -9.284 -2.543 1.009.72 B c
ATOM 6287 OG SERH409 -26.279 -8.269 -2.491 1.0010.75 B o
ATOM 6288 C SERH409 -27.686 -11.747 -2.596 1.009.01 B c
ATOM 6289 O SERH409 -28.360 -12.203 -1.671 1.009.02 B o
ATOM 6290 N LEU H 410 -27.804 -12.160 -3.853 1.00 8.91 B N
ATOM 6291 CA LEU H 410 -28.962-12.921 -4.302 1.009.29 B c
ATOM 6292 CB LEU H 410 -29.901 -12.033 -5.118 1.009.61 B c
ATOM 6293 CG LEU H 410 -31.317 -11.873 -4.558 1.009.70 B c
ATOM 6294 CD1 LEU H 410 -31.289 -11.183 -3.203 1.0011.11 B c
ATOM 6295 CD2LEUH410 -32.204 -11.113 -5.532 1.009.16 B c
ATOM 6296 C LEU H 410 -28.533 -14.134 -5.119 1.009.12 B c
ATOM 6297 O LEU H 410 -29.364-14.840 -5.690 1.009.08 B o
ATOM 6298 N GLY H 411 -27.228 -14.365 -5.173 1.009.03 B N
ATOM 6299 CA GLY H 411 -26.691 -15.606 -5.706 1.008.44 B c
ATOM 6300 C GLY H 411 -25.180 -15.615 -5.632 1.007.91 B c
ATOM 6301 O GLY H 411 -24.594 -15.123 -4.668 1.007.85 B o
ATOM 6302 N ALA H 412 -24.546-16.095 -6.694 1.007.30 B N
ATOM 6303 CA ALA H 412 -23.095 -16.167 -6.738 1.006.92 B c
ATOM 6304 CB ALA H 412 -22.607 -17.439 -6.062 1.006.90 B c
ATOM 6305 C ALA H 412 -22.593 -16.098 -8.173 1.006.99 B c
ATOM 6306 O ALA H 412 -23.277 -16.525 -9.102 1.00 6.94 B o
ATOM 6307 N ILEH413 -21.415 -15.510 -8.349 1.007.29 B N
ATOM 6308 CA ILEH413 -20.705 -15.567 -9.622 1.007.49 B c
ATOM 6309 CB ILEH413 -20.073 -14.207 -9.961 1.007.24 B c
ATOM 6310 CGI ILEH413 -21.142-13.236-10.466 1.007.18 B c
ATOM 6311 CD1 ILEH413 -20.589 -12.045 -11.233 1.007.70 B c
ATOM 6312 CG2ILEH413 -18.958 -14.377 -10.983 1.007.70 B c
ATOM 6313 C ILEH413 -19.596 -16.608 -9.554 1.007.94 B C
ATOM 6314 O ILEH413 -18.965 -16.775 -8.512 1.008.39 B O
ATOM 6315 N VAL H 414 -19.276 -17.221 -10.687 1.008.22 B N
ATOM 6316 CA VAL H 414 -18.141 -18.134 -10.734 1.008.77 B c
ATOM 6317 CB VAL H 414 -18.558 -19.593 -10.482 1.008.57 B c
ATOM 6318 CGI VAL H 414 -19.806 -19.936 -11.279 1.009.12 B ; C
ATOM 6319 CG2 VAL H 414 -17.416 -20.538 -10.825 1.008.90 B ; C
ATOM 6320 C VAL H 414 -17.323 -18.031 -12.015 1.008.92 B c
ATOM 6321 O VAL H 414 -17.803 -18.347 -13.105 1.009.00 B o
ATOM 6322 N SERH415 -16.058 -17.659 -11.853 1.008.97 B N
ATOM 6323 CA SERH415 -15.120-17.594-12.962 1.009.02 B c
ATOM 6324 CB SERH415 -14.260 -16.335 -12.855 1.008.98 B c
ATOM 6325 OG SERH415 -15.043 -15.218 -12.473 1.009.54 B o
ATOM 6326 C SERH415 -14.235 -18.832 -12.987 1.009.36 B c
ATOM 6327 O SERH415 -13.326 -18.975 -12.170 1.009.61 B o
ATOM 6328 N CYS H 416 -14.602 -19.786 -13.834 1.009.57 B N
ATOM 6329 CA CYS H 416 -13.851 -21.023 -13.963 1.009.61 B c
ATOM 6330 CB CYS H 416 -14.801 -22.216-14.038 1.009.62 B c
ATOM 6331 SG CYS H 416 -14.118 -23.727 -13.341 1.0011.33 B s
ATOM 6332 C CYS H 416 -12.998 -20.973 -15.215 1.009.61 B c
ATOM 6333 O CYS H 416 -13.519 -20.829 -16.320 1.009.80 B o
ATOM 6334 N TYRH417 -11.684-20.941 -15.027 1.009.48 B N
ATOM 6335 CA TYRH417 -10.772-20.739 -16.142 1.009.28 B c
ATOM 6336 CB TYRH417 -10.307 -19.281 -16.205 1.009.17 B c
ATOM 6337 CG TYRH417 -11.358 -18.318 -16.714 1.008.71 B c
ATOM 6338 CD1 TYRH417 -11.483 -17.048 -16.167 1.008.54 B c
ATOM 6339 CE1 TYRH417 -12.425 -16.159 -16.635 1.009.56 B c
ATOM 6340 CZ TYRH417 -13.230 -16.516 -17.693 1.009.83 B c
ATOM 6341 OH TYRH417 -14.184 -15.638 -18.143 1.0010.51 B ; O ATOM 6342 CE2 TY H 417 -13.122 -17.765 -18.263 1.00 9.36 B C
ATOM 6343 CD2 TY H 417 -12.177 -18.651 -17.786 1.00 8.95 B C
ATOM 6344 C TYR H 417 -9.572 -21.677 -16.068 1.00 9.35 B c
ATOM 6345 O TYR H 417 -9.336 -22.318 -15.044 1.00 9.11 B o
ATOM 6346 N GLY H 418 -8.830 -21.762 -17.169 1.00 9.71 B N
ATOM 6347 CA GLY H 418 -7.678 -22.656 -17.263 1.00 9.95 B c
ATOM 6348 C GLY H 418 -8.045 -24.101 -16.993 1.00 10.09 B c
ATOM 6349 O GLY H 418 -9.082 -24.584 -17.450 1.00 10.17 B o
ATOM 6350 N LYS H 419 -7.251 -24.756 -16.154 1.00 10.17 B N
ATOM 6351 CA LYS H 419 -7.426 -26.177 -15.896 1.00 10.50 B c
ATOM 6352 CB LYS H 419 -6.086 -26.827 -15.545 1.00 11.09 B c
ATOM 6353 CG LYS H 419 -5.332 -27.389 -16.738 1.00 12.94 B c
ATOM 6354 CD LYS H 419 -4.265 -28.377 -16.297 1.00 15.52 B c
ATOM 6355 CE LYS H 419 -3.705 -29.152 -17.479 1.00 17.07 B c
ATOM 6356 NZ LYS H 419 -3.179 -28.247 -18.538 1.00 19.30 B N
ATOM 6357 C LYS H 419 -8.447 -26.465 -14.798 1.00 10.23 B c
ATOM 6358 O LYS H 419 -8.613 -27.616 -14.398 1.00 10.58 B o
ATOM 6359 N THR H 420 -9.070 -25.426 -14.250 1.00 10.10 B N
ATOM 6360 CA THR H 420 -9.805 -25.587 -12.997 1.00 9.74 B c
ATOM 6361 CB THR H 420 -9.938 -24.270 -12.223 1.00 9.28 B c
ATOM 6362 OG1 THR H 420 -9.022 -23.306 -12.754 1.00 9.21 B o
ATOM 6363 CG2 THR H 420 -9.633 -24.499 -10.752 1.00 9.03 B c
ATOM 6364 C THR H 420 -11.181 -26.223 -13.168 1.00 9.95 B c
ATOM 6365 O THR H 420 -11.779 -26.160 -14.242 1.00 10.35 B o
ATOM 6366 N LYS H 421 -11.652 -26.879 -12.111 1.00 10.07 B N
ATOM 6367 CA LYS H 421 -12.961 -27.527 -12.115 1.00 10.21 B c
ATOM 6368 CB LYS H 421 -12.835 -28.979 -11.649 1.00 10.30 B c
ATOM 6369 CG LYS H 421 -12.705 -29.989 -12.776 1.00 12.43 B c
ATOM 6370 CD LYS H 421 -12.482 -31.391 -12.234 1.00 15.12 B c
ATOM 6371 CE LYS H 421 -11.769 -32.267 -13.251 1.00 15.21 B c
ATOM 6372 NZ LYS H 421 -11.047 -33.396 -12.601 1.00 15.98 B N
ATOM 6373 C LYS H 421 -13.933 -26.782 -11.206 1.00 10.09 B c
ATOM 6374 O LYS H 421 -13.600 -26.456 -10.067 1.00 10.36 B o
ATOM 6375 N CYS H 422 -15.155 -26.574 -11.685 1.00 9.81 B N
ATOM 6376 CA CYS H 422 -16.153 -25.863 -10.898 1.00 9.56 B c
ATOM 6377 CB CYS H 422 -16.222 -24.392 -11.302 1.00 9.72 B c
ATOM 6378 SG CYS H 422 -14.611 -23.591 -11.379 1.00 11.42 B s
ATOM 6379 C CYS H 422 -17.535 -26.499 -10.939 1.00 9.18 B c
ATOM 6380 O CYS H 422 -17.952 -27.056 -11.954 1.00 9.27 B o
ATOM 6381 N THR H 423 -18.273 -26.311 -9.851 1.00 8.93 B N
ATOM 6382 CA THR H 423 -19.417 -27.147 -9.527 1.00 8.64 B c
ATOM 6383 CB THR H 423 -19.014 -28.315 -8.606 1.00 8.32 B c
ATOM 6384 OG1 THR H 423 -17.878 -28.993 -9.154 1.00 7.97 B o
ATOM 6385 CG2 THR H 423 -20.165 -29.297 -8.456 1.00 8.36 B c
ATOM 6386 C THR H 423 -20.441 -26.297 -8.791 1.00 8.86 B c
ATOM 6387 O THR H 423 -20.133 -25.694 -7.763 1.00 9.26 B o
ATOM 6388 N ALA H 424 -21.676 -26.306 -9.279 1.00 8.74 B N
ATOM 6389 CA ALA H 424 -22.803 -25.836 -8.487 1.00 8.79 B c
ATOM 6390 CB ALA H 424 -23.693 -24.926 -9.317 1.00 8.94 B c
ATOM 6391 C ALA H 424 -23.605 -27.008 -7.932 1.00 8.84 B c
ATOM 6392 O ALA H 424 -24.158 -27.807 -8.687 1.00 9.24 B o
ATOM 6393 N SER H 425 -23.649 -27.113 -6.608 1.00 8.81 B N
ATOM 6394 CA SER H 425 -24.412 -28.166 -5.950 1.00 8.85 B c
ATOM 6395 CB SER H 425 -23.530 -28.925 -4.957 1.00 8.94 B c
ATOM 6396 OG SER H 425 -22.166 -28.871 -5.341 1.00 7.69 B o
ATOM 6397 C SER H 425 -25.626 -27.584 -5.235 1.00 9.01 B c
ATOM 6398 O SER H 425 -25.593 -26.447 -4.763 1.00 8.63 B o
ATOM 6399 N ASN H 426 -26.716 -28.345 -5.208 1.00 9.54 B N
ATOM 6400 CA ASN H 426 -27.971 -27.851 -4.658 1.00 10.19 B c
ATOM 6401 CB ASN H 426 -29.166 -28.508 -5.356 1.00 9.77 B c ATOM 6402 CG ASN H 426 -29.499 -29.874 -4.787 1.00 9.43 B C
ATOM 6403 OD1 ASN H 426 -28.998 -30.259 -3.730 1.00 9.01 B o
ATOM 6404 ND2 ASN H 426 -30.349 -30.615 -5.488 1.00 9.01 B N
ATOM 6405 C ASN H 426 -28.074 -28.031 -3.146 1.00 11.16 B C
ATOM 6406 O ASN H 426 -27.072 -28.247 -2.463 1.00 11.06 B o
ATOM 6407 N LYS H 427 -29.285 -27.847 -2.628 1.00 12.38 B N
ATOM 6408 CA LYS H 427 -29.569 -27.993 -1.203 1.00 13.52 B C
ATOM 6409 CB LYS H 427 -31.082 -28.017 -0.968 1.00 14.00 B c
ATOM 6410 CG LYS H 427 -31.681 -26.675 -0.585 1.00 16.18 B c
ATOM 6411 CD LYS H 427 -33.105 -26.838 -0.078 1.00 18.24 B c
ATOM 6412 CE LYS H 427 -33.487 -25.714 0.870 1.00 19.72 B c
ATOM 6413 NZ LYS H 427 -32.873 -25.888 2.216 1.00 21.43 B N
ATOM 6414 C LYS H 427 -28.943 -29.256 -0.621 1.00 13.71 B c
ATOM 6415 O LYS H 427 -28.329 -29.220 0.446 1.00 13.63 B o
ATOM 6416 N ASN H 428 -29.233 -30.390 -1.252 1.00 14.28 B N
ATOM 6417 CA ASN H 428 -28.838 -31.694 -0.729 1.00 14.60 B c
ATOM 6418 CB ASN H 428 -29.715 -32.800 -1.324 1.00 14.57 B c
ATOM 6419 CG ASN H 428 -31.103 -32.312 -1.690 1.00 13.24 B c
ATOM 6420 OD1 ASN H 428 -31.832 -31.790 -0.846 1.00 9.74 B o
ATOM 6421 ND2 ASN H 428 -31.503 -32.546 -2.935 1.00 12.83 B N
ATOM 6422 C ASN H 428 -27.367 -32.009 -0.984 1.00 14.83 B c
ATOM 6423 O ASN H 428 -26.834 -32.982 -0.451 1.00 15.25 B o
ATOM 6424 N ARG H 429 -26.755 -31.260 -1.895 1.00 14.78 B N
ATOM 6425 CA ARG H 429 -25.364 -31.488 -2.275 1.00 14.74 B c
ATOM 6426 CB ARG H 429 -24.626 -32.268 -1.184 1.00 14.93 B c
ATOM 6427 CG ARG H 429 -24.252 -31.435 0.031 1.00 16.26 B c
ATOM 6428 CD ARG H 429 -22.869 -30.821 -0.119 1.00 19.79 B c
ATOM 6429 NE ARG H 429 -22.634 -29.760 0.857 1.00 22.68 B N
ATOM 6430 CZ ARG H 429 -22.532 -29.958 2.167 1.00 23.54 B c
ATOM 6431 NHl ARG H 429 -22.640 -31.182 2.667 1.00 22.87 B N
ATOM 6432 NH2 ARG H 429 -22.321 -28.932 2.980 1.00 23.53 B N
ATOM 6433 C ARG H 429 -25.252 -32.217 -3.611 1.00 14.35 B C
ATOM 6434 O ARG H 429 -24.175 -32.285 -4.203 1.00 14.62 B o
ATOM 6435 N GLY H 430 -26.373 -32.752 -4.085 1.00 13.67 B N
ATOM 6436 CA GLY H 430 -26.519 -33.087 -5.496 1.00 12.80 B C
ATOM 6437 C GLY H 430 -26.014 -31.977 -6.397 1.00 12.11 B c
ATOM 6438 O GLY H 430 -26.326 -30.805 -6.188 1.00 12.18 B o
ATOM 6439 N ILE H 431 -25.216 -32.346 -7.393 1.00 11.58 B N
ATOM 6440 CA ILE H 431 -24.551 -31.372 -8.251 1.00 10.76 B c
ATOM 6441 CB ILE H 431 -23.175 -31.896 -8.715 1.00 10.43 B c
ATOM 6442 CGI ILE H 431 -22.220 -32.024 -7.527 1.00 10.95 B c
ATOM 6443 CD1 ILE H 431 -21.220 -33.153 -7.665 1.00 12.08 B c
ATOM 6444 CG2 ILE H 431 -22.592 -30.993 -9.791 1.00 10.07 B c
ATOM 6445 C ILE H 431 -25.406 -31.085 -9.484 1.00 10.68 B C
ATOM 6446 O ILE H 431 -25.703 -31.994 -10.258 1.00 10.40 B o
ATOM 6447 N ILE H 432 -25.852 -29.840 -9.636 1.00 10.90 B N
ATOM 6448 CA ILE H 432 -26.692 -29.481 -10.779 1.00 11.42 B c
ATOM 6449 CB ILE H 432 -27.709 -28.375 -10.448 1.00 11.63 B c
ATOM 6450 CGI ILE H 432 -27.875 -28.224 -8.936 1.00 12.68 B c
ATOM 6451 CD 1 ILE H 432 -28.514 -26.915 -8.524 1.00 13.89 B c
ATOM 6452 CG2 ILE H 432 -29.046 -28.664 -11.116 1.00 12.24 B c
ATOM 6453 C ILE H 432 -25.884 -29.045 -11.993 1.00 11.41 B c
ATOM 6454 O ILE H 432 -26.225 -29.395 -13.123 1.00 11.63 B o
ATOM 6455 N LYS H 433 -24.982 -28.093 -11.782 1.00 11.52 B N
ATOM 6456 CA LYS H 433 -24.226 -27.523 -12.888 1.00 11.96 B c
ATOM 6457 CB LYS H 433 -24.433 -26.010 -12.976 1.00 12.31 B c
ATOM 6458 CG LYS H 433 -23.850 -25.387 -14.237 1.00 14.42 B c
ATOM 6459 CD LYS H 433 -24.649 -24.175 -14.685 1.00 16.74 B c
ATOM 6460 CE LYS H 433 -24.112 -23.613 -15.993 1.00 17.08 B c
ATOM 6461 NZ LYS H 433 -24.993 -23.949 -17.146 1.00 17.30 B N ATOM 6462 C LYS H 433 -22.743 -27.850 -12.793 1.00 11.65 B C
ATOM 6463 O LYS H 433 -22.248 -28.250 -11.740 1.00 11.48 B O
ATOM 6464 N TH H 434 -22.052 -27.731 -13.921 1.00 11.28 B N
ATOM 6465 CA THR H 434 -20.617 -27.970 -13.975 1.00 11.21 B C
ATOM 6466 CB THR H 434 -20.308 -29.467 -14.165 1.00 11.30 B C
ATOM 6467 OG1 THR H 434 -18.945 -29.629 -14.574 1.00 11.83 B O
ATOM 6468 CG2 THR H 434 -21.224 -30.071 -15.220 1.00 11.84 B C
ATOM 6469 C THR H 434 -20.009 -27.185 -15.131 1.00 10.94 B C
ATOM 6470 O THR H 434 -20.623 -27.060 -16.190 1.00 10.93 B O
ATOM 6471 N PHE H 435 -18.867 -26.549 -14.886 1.00 11.10 B N
ATOM 6472 CA PHE H 435 -18.610 -25.235 -15.464 1.00 11.96 B C
ATOM 6473 CB PHE H 435 -18.186 -24.223 -14.401 1.00 11.51 B C
ATOM 6474 CG PHE H 435 -19.344 -23.561 -13.710 1.00 11.19 B C
ATOM 6475 CD 1 PHE H 435 -19.580 -23.788 -12.365 1.00 10.86 B C
ATOM 6476 CE1 PHE H 435 -20.692 -23.253 -11.741 1.00 10.24 B C
ATOM 6477 CZ PHE H 435 -21.613 -22.532 -12.474 1.00 9.89 B C
ATOM 6478 CE2 PHE H 435 -21.420 -22.347 -13.828 1.00 10.78 B C
ATOM 6479 CD2 PHE H 435 -20.304 -22.884 -14.445 1.00 11.14 B C
ATOM 6480 C PHE H 435 -17.694 -25.202 -16.684 1.00 13.00 B C
ATOM 6481 O PHE H 435 -16.525 -25.587 -16.618 1.00 13.03 B O
ATOM 6482 N SER H 436 -18.199 -24.569 -17.738 1.00 13.89 B N
ATOM 6483 CA SER H 436 -17.549 -24.549 -19.039 1.00 14.67 B C
ATOM 6484 CB SER H 436 -18.601 -24.438 -20.145 1.00 15.04 B C
ATOM 6485 OG SER H 436 -18.532 -25.539 -21.033 1.00 16.58 B O
ATOM 6486 C SER H 436 -16.586 -23.371 -19.134 1.00 14.75 B C
ATOM 6487 O SER H 436 -16.849 -22.398 -19.841 1.00 14.75 B O
ATOM 6488 N ASN H 437 -15.480 -23.451 -18.405 1.00 14.44 B N
ATOM 6489 CA ASN H 437 -14.306 -22.659 -18.736 1.00 14.35 B C
ATOM 6490 CB ASN H 437 -13.508 -23.354 -19.840 1.00 14.75 B C
ATOM 6491 CG ASN H 437 -12.101 -22.822 -19.966 1.00 15.51 B C
ATOM 6492 OD1 ASN H 437 -11.290 -22.960 -19.049 1.00 16.85 B O
ATOM 6493 ND2 ASN H 437 -11.757 -22.358 -21.162 1.00 16.10 B N
ATOM 6494 C ASN H 437 -14.692 -21.239 -19.161 1.00 13.69 B C
ATOM 6495 O ASN H 437 -14.402 -20.814 -20.280 1.00 13.40 B O
ATOM 6496 N GLY H 438 -15.374 -20.527 -18.267 1.00 13.39 B N
ATOM 6497 CA GLY H 438 -15.942 -19.216 -18.573 1.00 12.92 B C
ATOM 6498 C GLY H 438 -16.310 -18.455 -17.311 1.00 12.72 B C
ATOM 6499 O GLY H 438 -15.574 -18.495 -16.324 1.00 12.83 B O
ATOM 6500 N CYS H 439 -17.502 -17.863 -17.297 1.00 12.17 B N
ATOM 6501 CA CYS H 439 -17.969 -17.110 -16.134 1.00 11.52 B C
ATOM 6502 CB CYS H 439 -17.353 -15.712 -16.124 1.00 11.68 B C
ATOM 6503 SG CYS H 439 -18.500 -14.404 -16.619 1.00 12.89 B S
ATOM 6504 C CYS H 439 -19.492 -17.006 -16.079 1.00 10.95 B C
ATOM 6505 O CYS H 439 -20.102 -16.298 -16.880 1.00 10.77 B O
ATOM 6506 N ASP H 440 -20.089 -17.630 -15.066 1.00 10.41 B N
ATOM 6507 CA ASP H 440 -21.541 -17.762 -14.987 1.00 10.06 B C
ATOM 6508 CB ASP H 440 -21.953 -19.232 -15.091 1.00 10.85 B C
ATOM 6509 CG ASP H 440 -22.561 -19.576 -16.438 1.00 13.11 B C
ATOM 6510 OD1 ASP H 440 -23.750 -19.260 -16.654 1.00 14.97 B O
ATOM 6511 OD2 ASP H 440 -21.872 -20.227 -17.251 1.00 15.27 B O
ATOM 6512 C ASP H 440 -22.098 -17.161 -13.700 1.00 9.01 B C
ATOM 6513 O ASP H 440 -21.345 -16.790 -12.798 1.00 9.09 B O
ATOM 6514 N TYR H 441 -23.422 -17.184 -13.580 1.00 7.92 B N
ATOM 6515 CA TYR H 441 -24.117 -16.707 -12.387 1.00 7.24 B C
ATOM 6516 CB TYR H 441 -24.810 -15.371 -12.683 1.00 7.04 B C
ATOM 6517 CG TYR H 441 -25.669 -14.849 -11.556 1.00 6.77 B C
ATOM 6518 CD1 TYR H 441 -25.145 -13.986 -10.605 1.00 7.41 B C
ATOM 6519 CE1 TYR H 441 -25.927 -13.498 -9.579 1.00 6.79 B C
ATOM 6520 CZ TYR H 441 -27.270 -13.809 -9.539 1.00 6.49 B C
ATOM 6521 OH TYR H 441 -28.049 -13.340 -8.507 1.00 5.09 B O ATOM 6522 CE2 TY H 441 -27.823 -14.634 -10.494 1.00 7.52 B C
ATOM 6523 CD2 TYR H 441 -27.029 -15.122 -11.512 1.00 7.12 B C
ATOM 6524 C TYR H 441 -25.153 -17.748 -11.974 1.00 6.89 B c
ATOM 6525 O TYR H 441 -25.720 -18.436 -12.823 1.00 7.12 B o
ATOM 6526 N VAL H 442 -25.353 -17.906 -10.670 1.00 6.73 B N
ATOM 6527 CA VAL H 442 -26.400 -18.784 -10.159 1.00 6.78 B c
ATOM 6528 CB VAL H 442 -25.808 -20.089 -9.596 1.00 6.51 B c
ATOM 6529 CGI VAL H 442 -25.394 -21.017 -10.729 1.00 7.38 B , c
ATOM 6530 CG2 VAL H 442 -24.625 -19.786 -8.688 1.00 6.00 B c
ATOM 6531 C VAL H 442 -27.167 -18.062 -9.059 1.00 7.13 B c
ATOM 6532 O VAL H 442 -26.774 -16.973 -8.643 1.00 7.77 B o
ATOM 6533 N SER H 443 -28.229 -18.679 -8.552 1.00 7.12 B N
ATOM 6534 CA SER H 443 -29.017 -18.039 -7.504 1.00 7.64 B c
ATOM 6535 CB SER H 443 -30.184 -17.252 -8.104 1.00 7.83 B c
ATOM 6536 OG SER H 443 -31.411 -17.936 -7.922 1.00 7.99 B o
ATOM 6537 C SER H 443 -29.508 -18.989 -6.415 1.00 8.16 B c
ATOM 6538 O SER H 443 -29.421 -20.210 -6.552 1.00 8.69 B o
ATOM 6539 N ASN H 444 -29.959 -18.412 -5.306 1.00 8.73 B N
ATOM 6540 CA ASN H 444 -30.539 -19.184 -4.213 1.00 9.50 B c
ATOM 6541 CB ASN H 444 -30.766 -18.297 -2.984 1.00 9.65 B c
ATOM 6542 CG ASN H 444 -29.895 -17.053 -2.990 1.00 10.64 B c
ATOM 6543 OD1 ASN H 444 -28.780 -17.060 -3.516 1.00 12.28 B , o
ATOM 6544 ND2 ASN H 444 -30.414 -15.966 -2.426 1.00 11.75 B , N
ATOM 6545 C ASN H 444 -31.843 -19.863 -4.618 1.00 10.24 B c
ATOM 6546 O ASN H 444 -32.618 -19.317 -5.403 1.00 9.89 B o
ATOM 6547 N LYS H 445 -32.146 -20.975 -3.955 1.00 11.63 B N
ATOM 6548 CA LYS H 445 -32.826 -22.105 -4.588 1.00 13.07 B c
ATOM 6549 CB LYS H 445 -34.344 -21.990 -4.421 1.00 13.70 B c
ATOM 6550 CG LYS H 445 -35.131 -23.200 -4.915 1.00 15.80 B c
ATOM 6551 CD LYS H 445 -34.354 -24.501 -4.753 1.00 18.31 B c
ATOM 6552 CE LYS H 445 -33.508 -24.498 -3.490 1.00 19.03 B c
ATOM 6553 NZ LYS H 445 -34.316 -24.206 -2.274 1.00 20.02 B N
ATOM 6554 C LYS H 445 -32.459 -22.265 -6.060 1.00 12.96 B c
ATOM 6555 O LYS H 445 -32.290 -21.282 -6.780 1.00 13.24 B o
ATOM 6556 N GLY H 446 -32.350 -23.513 -6.504 1.00 13.08 B N
ATOM 6557 CA GLY H 446 -31.215 -23.936 -7.312 1.00 12.42 B c
ATOM 6558 C GLY H 446 -29.988 -24.163 -6.453 1.00 11.83 B c
ATOM 6559 O GLY H 446 -29.855 -25.209 -5.819 1.00 12.44 B o
ATOM 6560 N VAL H 447 -29.191 -23.114 -6.285 1.00 10.63 B N
ATOM 6561 CA VAL H 447 -27.809 -23.277 -5.857 1.00 10.01 B c
ATOM 6562 CB VAL H 447 -26.839 -22.442 -6.711 1.00 9.97 B c
ATOM 6563 CGI VAL H 447 -25.405 -22.896 -6.479 1.00 10.51 B , c
ATOM 6564 CG2 VAL H 447 -27.204 -22.551 -8.183 1.00 10.50 B , c
ATOM 6565 C VAL H 447 -27.603 -22.962 -4.380 1.00 9.53 B c
ATOM 6566 O VAL H 447 -28.099 -21.957 -3.868 1.00 9.61 B o
ATOM 6567 N ASP H 448 -26.719 -23.735 -3.760 1.00 9.16 B N
ATOM 6568 CA ASP H 448 -26.522 -23.714 -2.318 1.00 8.75 B c
ATOM 6569 CB ASP H 448 -27.139 -24.971 -1.698 1.00 9.22 B c
ATOM 6570 CG ASP H 448 -27.482 -24.795 -0.234 1.00 11.44 B c
ATOM 6571 OD1 ASP H 448 -26.877 -23.921 0.421 1.00 13.83 B o
ATOM 6572 OD2 ASP H 448 -28.319 -25.568 0.276 1.00 14.13 B o
ATOM 6573 C ASP H 448 -25.020 -23.714 -2.076 1.00 8.18 B c
ATOM 6574 O ASP H 448 -24.528 -23.151 -1.098 1.00 8.06 B o
ATOM 6575 N THR H 449 -24.298 -24.280 -3.036 1.00 7.63 B N
ATOM 6576 CA THR H 449 -22.858 -24.437 -2.940 1.00 6.80 B c
ATOM 6577 CB THR H 449 -22.485 -25.824 -2.386 1.00 6.89 B c
ATOM 6578 OG1 THR H 449 -22.377 -25.758 -0.959 1.00 6.16 B o
ATOM 6579 CG2 THR H 449 -21.163 -26.296 -2.970 1.00 7.55 B c
ATOM 6580 C THR H 449 -22.265 -24.297 -4.333 1.00 6.53 B c
ATOM 6581 O THR H 449 -22.828 -24.792 -5.309 1.00 6.59 B o ATOM 6582 N VAL H 450 -21.145 -23.594■ -4.428 1.00 6.07 B N
ATOM 6583 CA VAL H 450 -20.209 -23.829 -5.512 1.00 6.02 B C
ATOM 6584 CB VAL H 450 -20.064 -22.597 -6.420 1.00 5.61 B C
ATOM 6585 CGI VAL H 450 -21.429 -22.130 -6.904 1.00 5.32 B c
ATOM 6586 CG2 VAL H 450 -19.339 -21.481 -5.687 1.00 5.55 B c
ATOM 6587 C VAL H 450 -18.853 -24.210 - ■4.950 1.00 6.37 B c
ATOM 6588 O VAL H 450 -18.503 -23.827 ■ -3.833 1.00 6.54 B o
ATOM 6589 N SE H 451 -18.176 -25.110 - 5.649 1.00 6.41 B N
ATOM 6590 CA SER H 451 -16.786 -25.397 -5.362 1.00 6.70 B c
ATOM 6591 CB SER H 451 -16.602 -26.886 -5.069 1.00 7.13 B c
ATOM 6592 OG SER H 451 -17.729 -27.629 -5.498 1.00 9.26 B o
ATOM 6593 C SER H 451 -15.944 -24.990 - 6.555 1.00 6.47 B c
ATOM 6594 O SER H 451 -16.363 -25.147 - 7.701 1.00 6.54 B o
ATOM 6595 N VAL H 452 -14.861 -24.277 ■ -6.276 1.00 6.56 B N
ATOM 6596 CA VAL H 452 -13.801 -24.112 -7.251 1.00 6.31 B c
ATOM 6597 CB VAL H 452 -13.469 -22.625 -7.471 1.00 5.74 B c
ATOM 6598 CGI VAL H 452 -12.757 -22.433 -8.801 1.00 5.06 B c
ATOM 6599 CG2 VAL H 452 -14.740 -21.787 -7.420 1.00 5.56 B c
ATOM 6600 C VAL H 452 -12.558 -24.861 - -6.791 1.00 6.60 B c
ATOM 6601 O VAL H 452 -12.130 -24.726■ -5.644 1.00 7.04 B o
ATOM 6602 N GLY H 453 -12.047 -25.732■ -7.654 1.00 6.54 B N
ATOM 6603 CA GLY H 453 -11.013 -26.672 -7.250 1.00 6.43 B c
ATOM 6604 C GLY H 453 -11.329 -27.255 - -5.889 1.00 6.09 B c
ATOM 6605 O GLY H 453 -12.396 -27.836■ -5.690 1.00 5.90 B o
ATOM 6606 N ASN H 454 -10.479 -26.962 - -4.913 1.00 6.02 B N
ATOM 6607 CA ASN H 454 -10.646 -27.533 -3.585 1.00 6.39 B c
ATOM 6608 CB ASN H 454 -9.330 -28.111 -3.073 1.00 6.81 B c
ATOM 6609 CG ASN H 454 -9.190 -29.585 -3.382 1.00 8.99 B c
ATOM 6610 OD1 ASN H 454 -9.587 -30.433 -2.584 1.00 11.67 B o
ATOM 6611 ND2 ASN H 454 -8.782 -29.893 -4.609 1.00 10.25 B N
ATOM 6612 C ASN H 454 -11.235 -26.563 - 2.573 1.00 6.15 B c
ATOM 6613 O ASN H 454 -11.623 -26.963 - -1.475 1.00 6.47 B o
ATOM 6614 N THR H 455 -11.406 -25.312 - -2.985 1.00 5.40 B N
ATOM 6615 CA THR H 455 -12.129 -24.347 -2.172 1.00 4.53 B c
ATOM 6616 CB THR H 455 -11.775 -22.902 -2.551 1.00 4.70 B c
ATOM 6617 OG1 THR H 455 -10.351 -22.746 -2.567 1.00 5.28 B o
ATOM 6618 CG2 THR H 455 -12.374 -21.928 -1.542 1.00 5.57 B c
ATOM 6619 C THR H 455 -13.632 -24.543 - 2.293 1.00 4.01 B c
ATOM 6620 O THR H 455 -14.139 -24.921 - -3.349 1.00 3.78 B o
ATOM 6621 N LEU H 456 -14.338 -24.306 - 1.194 1.00 3.87 B N
ATOM 6622 CA LEU H 456 -15.787 -24.419 -1.181 1.00 4.05 B c
ATOM 6623 CB LEU H 456 -16.232 -25.520 -0.219 1.00 3.95 B c
ATOM 6624 CG LEU H 456 -17.708 -25.915 -0.306 1.00 3.76 B c
ATOM 6625 CD1 LEU H 456 -18.042 -26.440 -1.694 1.00 5.35 B c
ATOM 6626 CD2 LEU H 456 -18.053 -26.944 0.758 1.00 4.10 B c
ATOM 6627 C LEU H 456 -16.439 -23.097 - 0.802 1.00 4.47 B c
ATOM 6628 O LEU H 456 -16.186 -22.551 0.272 1.00 4.94 B o
ATOM 6629 N TYR H 457 -17.343 -22.634 - -1.657 1.00 4.59 B N
ATOM 6630 CA TYR H 457 -18.102 -21.425 -1.386 1.00 4.60 B c
ATOM 6631 CB TYR H 457 -17.996 -20.463 -2.570 1.00 4.71 B c
ATOM 6632 CG TYR H 457 -16.594 -19.949 -2.820 1.00 5.62 B c
ATOM 6633 CD1 TYR H 457 -15.657 -20.727 -3.485 1.00 7.09 B c
ATOM 6634 CE1 TYR H 457 -14.388 -20.247 -3.748 1.00 8.22 B c
ATOM 6635 CZ TYR H 457 -14.029 -18.994 -3.305 1.00 8.06 B c
ATOM 6636 OH TYR H 457 -12.763 -18.520 -3.550 1.00 8.80 B o
ATOM 6637 CE2 TYR H 457 -14.933 -18.212 -2.622 1.00 7.18 B c
ATOM 6638 CD2 TYR H 457 -16.203 -18.694 -2.375 1.00 6.66 B c
ATOM 6639 C TYR H 457 -19.565 -21.758 - 1.099 1.00 4.46 B c
ATOM 6640 O TYR H 457 -20.180 -22.551 - -1.811 1.00 4.92 B o
ATOM 6641 N TYR H 458 -20.098 -21.196 - -0.017 1.00 3.90 B N ATOM 6642 CA TY H 458 -21.496 -21.408 0.366 1.00 3.26 B C
ATOM 6643 CB TYR H 458 -21.610 -21.544 1.885 1.00 3.16 B C
ATOM 6644 CG TYR H 458 -20.863 -22.722 2.457 1.00 3.29 B c
ATOM 6645 CD1 TYR H 458 -19.547 -22.597 2.881 1.00 3.93 B c
ATOM 6646 CE1 TYR H 458 -18.866 -23.672 3.419 1.00 4.90 B c
ATOM 6647 CZ TYR H 458 -19.501 -24.890 3.535 1.00 5.12 B c
ATOM 6648 OH TYR H 458 -18.826 -25.967 4.062 1.00 5.42 B o
ATOM 6649 CE2 TYR H 458 -20.810 -25.036 3.128 1.00 4.72 B c
ATOM 6650 CD2 TYR H 458 -21.483 -23.955 2.598 1.00 3.89 B c
ATOM 6651 C TYR H 458 -22.372 -20.242 - ■0.085 1.00 3.04 B c
ATOM 6652 O TYR H 458 -22.185 -19.119 0.378 1.00 3.37 B 0
ATOM 6653 N VAL H 459 -23.453 -20.542 -0.800 1.00 2.71 B N
ATOM 6654 CA VAL H 459 -24.073 -19.546 -1.678 1.00 2.61 B c
ATOM 6655 CB VAL H 459 -24.381 -20.115 -3.067 1.00 2.22 B c
ATOM 6656 CGI VAL H 459 -25.021 -19.042 -3.938 1.00 2.62 B c
ATOM 6657 CG2 VAL H 459 -23.123 -20.656 -3.716 1.00 2.61 B c
ATOM 6658 C VAL H 459 -25.372 -18.924■ -1.190 1.00 3.03 B c
ATOM 6659 O VAL H 459 -25.418 -18.348 -0.103 1.00 3.21 B o
ATOM 6660 N ASN H 460 -26.215 -18.648 ■ -2.185 1.00106.93 B N
ATOM 6661 CA ASN H 460 -27.625 -18.431 -1.941 1.00 95.54 B c
ATOM 6662 CB ASN H 460 -27.810 -17.878 -0.542 1.00 20.00 B c
ATOM 6663 CG ASN H 460 -28.967 -18.507 0.162 1.00 20.00 B c
ATOM 6664 ODl ASN H 460 -29.655 -19.349 -0.416 1.00 20.00 B o
ATOM 6665 ND2 ASN H 460 -29.359 -17.912 1.280 1.00 20.00 B N
ATOM 6666 C ASN H 460 -28.426 -17.612 - ■2.969 1.00 99.41 B c
ATOM 6667 O ASN H 460 -29.222 -18.178 ■ -3.718 1.00108.91 B o
ATOM 6668 N LYS H 461 -28.370 -16.283 - 2.861 1.00 97.04 B N
ATOM 6669 CA LYS H 461 -29.458 -15.387 -3.306 1.00105.93 B c
ATOM 6670 CB LYS H 461 -29.011 -13.925 -3.219 1.00 20.00 B c
ATOM 6671 CG LYS H 461 -28.633 -13.460 -1.820 1.00 20.00 B c
ATOM 6672 CD LYS H 461 -27.794 -12.187 -1.865 1.00 20.00 B c
ATOM 6673 CE LYS H 461 -27.646 -11.565 -0.482 1.00 20.00 B c
ATOM 6674 NZ LYS H 461 -26.746 -10.375 -0.482 1.00 20.00 B N
ATOM 6675 C LYS H 461 -30.025 -15.676 - 4.708 1.00102.28 B c
ATOM 6676 O LYS H 461 -29.779 -16.739 - 5.276 1.00105.02 B o
ATOM 6677 N GLN H 462 -30.766 -14.715 -5.266 1.00 96.68 B N
ATOM 6678 CA GLN H 462 -31.286 -14.810 -6.641 1.00105.71 B c
ATOM 6679 CB GLN H 462 -32.787 -15.128 -6.624 1.00 20.00 B c
ATOM 6680 CG GLN H 462 -33.142 -16.522 -6.122 1.00 20.00 B c
ATOM 6681 CD GLN H 462 -34.637 -16.794 -6.159 1.00 20.00 B c
ATOM 6682 OE1 GLN H 462 -35.450 -15.870 -6.115 1.00 20.00 B o
ATOM 6683 NE2 GLN H 462 -35.006 -18.068 -6.230 1.00 20.00 B N
ATOM 6684 C GLN H 462 -31.052 -13.514■ -7.429 1.00101.50 B c
ATOM 6685 O GLN H 462 -31.398 -12.430 -6.960 1.00105.94 B o
ATOM 6686 N GLU H 463 -30.565 -13.634 -8.663 1.00 98.92 B N
ATOM 6687 CA GLU H 463 -30.241 -12.453 -9.465 1.00108.59 B c
ATOM 6688 CB GLU H 463 -28.792 -12.505 -9.966 1.00 20.00 B c
ATOM 6689 CG GLU H 463 -27.767 -11.973 -8.957 1.00 20.00 B c
ATOM 6690 CD GLU H 463 -26.341 -11.973 -9.490 1.00 20.00 B c
ATOM 6691 OE1 GLU H 463 -26.167 -11.917 -10.729 1.00 20.00 E ; o
ATOM 6692 OE2 GLU H 463 -25.399 -11.890 -8.672 1.00 20.00 B o
ATOM 6693 C GLU H 463 -31.208 -12.245 - 10.629 1.00116.39 B c
ATOM 6694 O GLU H 463 -31.442 -13.153 - 11.426 1.00118.70 B o
ATOM 6695 N GLY H 464 -31.759 -11.039 - 10.722 1.00127.70 B N
ATOM 6696 CA GLY H 464 -32.671 -10.693 -11.806 1.00143.17 B C
ATOM 6697 C GLY H 464 -31.941 -10.347 - 13.089 1.00149.77 B C
ATOM 6698 O GLY H 464 -30.719 -10.197 - 13.098 1.00155.06 B o
ATOM 6699 N LYS H 465 -32.694 -10.223 -: L4.178 1.00153.73 B N
ATOM 6700 CA LYS H 465 -32.115 -9.929 - 15.484 1.00153.69 B C
ATOM 6701 CB LYS H 465 -31.275 -8.651 - 15.424 1.00 20.00 B c ATOM 6702 CG LYS H 465 -32.085 -7.385 -15.193 1.00 20.00 B C ATOM 6703 CD LYS H 465 -31.186 -6.163 -15.106 1.00 20.00 B C ATOM 6704 CE LYS H 465 -31.995 -4.898 -14.868 1.00 20.00 B C ATOM 6705 NZ LYS H 465 -31.127 -3.692 -14.776 1.00 20.00 B N ATOM 6706 C LYS H 465 -31.267 -11.091 - 15.990 1.00155.37 B C ATOM 6707 O LYS H 465 -31.276 -11.407■■17.180 1.00155.20 B O ATOM 6708 N GLU H 472 -30.692 -9.899 - 23.132 1.00145.47 B N ATOM 6709 CA GLU H 472 -30.214 -9.535 -24.461 1.00151.12 B C ATOM 6710 CB GLU H 472 -30.931 8.281 -24.964 1.00 20.00 B C ATOM 6711 CG GLU H 472 -32.419 8.472 -25.209 1.00 20.00 B C ATOM 6712 CD GLU H 472 -33.106 7.192 -25.643 1.00 20.00 B C ATOM 6713 OE1 GLU H 472 -32.477 -6.117 25.554 1.00 20.00 B O ATOM 6714 OE2 GLU H 472 -34.279 -7.260 26.070 1.00 20.00 B O ATOM 6715 C GLU H 472 -28.705 -9.310 24.462 1.00153.35 B C ATOM 6716 O GLU H 472 -28.208 -8.395 23.805 1.00159.41 B O ATOM 6717 N PRO H 473 -27.971 -10.164 -25.188 1.00150.51 B N ATOM 6718 CA PRO H 473 -26.535 -10.028 -25.339 1.00141.97 B C ATOM 6719 CB PRO H 473 -26.035 -11.435 -25.011 1.00 20.00 B C ATOM 6720 CG PRO H 473 -27.175 -12.350 -25.428 1.00 20.00 B C ATOM 6721 CD PRO H 473 -28.424 -11.506 -25.583 1.00 20.00 B C ATOM 6722 C PRO H 473 -26.193 -9.688 -26.782 1.00135.14 B C ATOM 6723 O PRO H 473 -26.968 -9.997 -27.687 1.00144.93 B O ATOM 6724 N ILE H 474 25.024 -9.096 -27.001 1.00118.07 B N ATOM 6725 CA ILE H 474 -24.617 -8.700 -28.344 1.00105.14 B C ATOM 6726 CB ILE H 474 -25.549 -7.614 -28.919 1.00 20.00 B C ATOM 6727 CGI ILE H 474 -26.957 -8.174 -29.133 1.00 20.00 B C ATOM 6728 CD1 ILE H 474 -28.021 -7.109 -29.293 1.00 20.00 B C ATOM 6729 CG2 ILE H 474 -24.988 -7.064 -30.222 1.00 20.00 B C ATOM 6730 C ILE H 474 23.184 -8.180 -28.352 1.00104.75 B C ATOM 6731 O ILE H 474 22.938 -7.013 -28.046 1.00111.83 B O ATOM 6732 N ILE H 475 22.242 -9.045 -28.716 1.00 94.65 B N ATOM 6733 CA ILE H 475 -20.826 -8.732 -28.565 1.00 79.88 B C ATOM 6734 CB ILE H 475 -20.175 -9.577 -27.453 1.00 20.00 B C ATOM 6735 CGI ILE H 475 -20.674 -9.120 -26.079 1.00 20.00 B C ATOM 6736 CD1 ILE H 475 -20.434 -10.125 -24.972 1.00 20.00 B C ATOM 6737 CG2 ILE H 475 -18.658 -9.507 -27.545 1.00 20.00 B C ATOM 6738 C ILE H 475 20.051 -8.909 -29.868 1.00 79.52 B C ATOM 6739 O ILE H 475 19.808 -10.032 -30.310 1.00 82.70 B O ATOM 6740 N ASN H 476 -19.589 -7.793 -30.425 1.00 69.64 B N ATOM 6741 CA ASN H 476 -18.756 -7.812 -31.623 1.00 68.88 B C ATOM 6742 CB ASN H 476 -18.880 - 6.487 -32.381 1.00 20.00 B C ATOM 6743 CG ASN H 476 -20.247 -■6.299 -33.011 1.00 20.00 B C ATOM 6744 OD1 ASN H 476 -20.954 -7.268 -33.288 1.00 20.00 B O ATOM 6745 ND2 ASN H 476 -20.618 -5.048 -33.257 1.00 20.00 B N ATOM 6746 C ASN H 476 -17.290 -■8i .097 -31.306 1.00 67.13 B C ATOM 6747 O ASN H 476 -16.718 - -7.507 -30.389 1.00 73.10 B O ATOM 6748 N PHE H 477 -16.677 - 8.975 -32.096 1.00 64.95 B N ATOM 6749 CA PHE H 477 -15.288 -9.380 -31.879 1.00 68.13 B C ATOM 6750 CB PHE H 477 -14.918 - -10.567 -32.776 1.00 20.00 B C ATOM 6751 CG PHE H 477 -15.678 -11.822 -32.466 1.00 20.00 B C ATOM 6752 CD1 PHE H 477 -15.266 - 12.666 -31.448 1.00 20.00 B C ATOM 6753 CE1 PHE H 477 -15.965 - 13.820 -31.162 1.00 20.00 B C ATOM 6754 CZ PHE H 477 -17.069 14.158 -31.915 1.00 20.00 B C ATOM 6755 CE2 PHE H 477 -17.473 - 13.339 -32.949 1.00 20.00 B C ATOM 6756 CD2 PHE H 477 -16.778■ 12.181 -33.222 1.00 20.00 B C ATOM 6757 C PHE H 477 -14.307 8.232 -32.117 1.00 65.57 B C ATOM 6758 O PHE H 477 -13.094 -8.412 -31.999 1.00 49.83 B O ATOM 6759 N TYR H 478 -14.816 -7.113 -32.617 1.00 51.97 B N ATOM 6760 CA TYR H 478 -13.996 -5.920 -32.779 1.00 52.01 B C ATOM 6761 CB TYR H 478 -14.573 -5.017 -33.870 1.00 20.00 B C ATOM 6762 CG TY H 478 -14.579 -5.653 -35.247 1.00 20.00 B C
ATOM 6763 CD1 TYR H 478 -13.458 -5.593 -36.069 1.00 20.00 B C
ATOM 6764 CE1 TYR H 478 -13.453 -6.195 -37.316 1.00 20.00 B C
ATOM 6765 CZ TYR H 478 -14.585 -6.849 -37.766 1.00 20.00 B C
ATOM 6766 OH TYR H 478 -14.597 -7.434 -39.013 1.00 20.00 B O
ATOM 6767 CE2 TYR H 478 -15.689 -6.967 -36.948 1.00 20.00 B C
ATOM 6768 CD2 TYR H 478 -15.687 -6.360 -35.703 1.00 20.00 B C
ATOM 6769 C TYR H 478 -13.909 -5.178 -31.454 1.00 66.63 B C
ATOM 6770 O TYR H 478 -13.401 -4.059 -31.383 1.00 63.45 B O
ATOM 6771 N ASP H 479 -14.391 -5.828 -30.401 1.00 65.34 B N
ATOM 6772 CA ASP H 479 -14.256 -5.311 -29.049 1.00 65.32 B C
ATOM 6773 CB ASP H 479 -15.579 -5.450 -28.296 1.00 20.00 B C
ATOM 6774 CG ASP H 479 -16.664 -4.552 -28.856 1.00 20.00 B C
ATOM 6775 OD1 ASP H 479 -16.327 -3.593 -29.582 1.00 20.00 B O
ATOM 6776 OD2 ASP H 479 -17.854 -4.799 -28.568 1.00 20.00 B O
ATOM 6777 C ASP H 479 -13.144 -6.036 -28.300 1.00 64.83 B C
ATOM 6778 O ASP H 479 -12.738 -5.609 -27.220 1.00 60.42 B O
ATOM 6779 N PRO H 480 -12.610 -7.108 -28.903 1.00 47.60 B N
ATOM 6780 CA PRO H 480 -11.568 -7.902 -28.282 1.00 46.52 B C
ATOM 6781 CB PRO H 480 -11.905 -9.318 -28.742 1.00 20.00 B C
ATOM 6782 CG PRO H 480 -12.596 -9.131 -30.072 1.00 20.00 B C
ATOM 6783 CD PRO H 480 -13.021 -7.682 -30.193 1.00 20.00 B C
ATOM 6784 C PRO H 480 -10.199 -7.497 -28.809 1.00 52.36 B C
ATOM 6785 O PRO H 480 -9.736 -8.035 -29.815 1.00 64.15 B O
ATOM 6786 N LEU H 481 -9.618 -6.472 -28.197 1.00 62.90 B N
ATOM 6787 CA LEU H 481 -8.285 -6.015 -28.562 1.00 54.24 B C
ATOM 6788 CB LEU H 481 -8.322 -4.544 -28.982 1.00 20.00 B C
ATOM 6789 CG LEU H 481 -9.202 -4.212 -30.186 1.00 20.00 B C
ATOM 6790 CD 1 LEU H 481 -9.255 -2.706 -30.408 1.00 20.00 B C
ATOM 6791 CD2 LEU H 481 -8.698 -4.931 -31.425 1.00 20.00 B C
ATOM 6792 C LEU H 481 -7.315 -6.203 -27.402 1.00 59.81 B C
ATOM 6793 O LEU H 481 -7.682 -6.724 -26.348 1.00 64.98 B O
ATOM 6794 N VAL H 482 -6.058 -5.840 -27.628 1.00 59.66 B N
ATOM 6795 CA VAL H 482 -5.084 -5.781 -26.549 1.00 49.67 B C
ATOM 6796 CB VAL H 482 -3.786 -6.531 -26.911 1.00 20.00 B C
ATOM 6797 CGI VAL H 482 -2.811 -6.492 -25.742 1.00 20.00 B C
ATOM 6798 CG2 VAL H 482 -4.097 -7.973 -27.288 1.00 20.00 B C
ATOM 6799 C VAL H 482 -4.762 -4.337 -26.191 1.00 53.03 B C
ATOM 6800 O VAL H 482 -4.706 -3.472 -27.064 1.00 46.27 B O
ATOM 6801 N PHE H 483 -4.641 -4.070 -24.894 1.00 61.61 B N
ATOM 6802 CA PHE H 483 -4.311 -2.732 -24.415 1.00 65.03 B C
ATOM 6803 CB PHE H 483 -5.338 -2.259 -23.391 1.00 20.00 B C
ATOM 6804 CG PHE H 483 -6.714 -2.064 -23.966 1.00 20.00 B C
ATOM 6805 CD1 PHE H 483 -7.021 -0.928 -24.695 1.00 20.00 B C
ATOM 6806 CE1 PHE H 483 -8.294 -0.739 -25.209 1.00 20.00 B C
ATOM 6807 CZ PHE H 483 -9.246 -1.731 -25.077 1.00 20.00 B C
ATOM 6808 CE2 PHE H 483 -8.937 -2.888 -24.397 1.00 20.00 B C
ATOM 6809 CD2 PHE H 483 -7.667 -3.065 -23.872 1.00 20.00 B C
ATOM 6810 C PHE H 483 -2.897 -2.662 -23.852 1.00 71.00 B C
ATOM 6811 O PHE H 483 -2.704 -2.417 -22.659 1.00100.44 B O
ATOM 6812 N PRO H 484 -1.909 -2.972 -24.705 1.00 54.44 B N
ATOM 6813 CA PRO H 484 -0.512 -3.000 -24.329 1.00 47.46 B C
ATOM 6814 CB PRO H 484 -0.179 -4.492 -24.438 1.00 20.00 B C
ATOM 6815 CG PRO H 484 -1.142 -5.021 -25.513 1.00 20.00 B C
ATOM 6816 CD PRO H 484 -2.157 -3.926 -25.796 1.00 20.00 B C
ATOM 6817 C PRO H 484 0.323 -2.225 -25.346 1.00 41.56 B C
ATOM 6818 O PRO H 484 0.278 -2.527 -26.539 1.00 46.53 B O
ATOM 6819 N SER H 485 1.033 -1.202 -24.883 1.00 46.30 B N
ATOM 6820 CA SER H 485 1.824 -0.355 -25.768 1.00 49.30 B C
ATOM 6821 CB SER H 485 3.010 0.252 -25.015 1.00 20.00 B C ATOM 6822 OG SE H 485 3.864 -0.754 -24.502 1.00 20.00 B O
ATOM 6823 C SER H 485 2.307 -1.112 -27.003 1.00 41.24 B C
ATOM 6824 O SER H 485 1.964 -0.755 -28.131 1.00 46.93 B O
ATOM 6825 N ASP H 486 3.108 -2.150 -26.785 1.00 49.48 B N
ATOM 6826 CA ASP H 486 3.700 -2.909 -27.881 1.00 37.44 B C
ATOM 6827 CB ASP H 486 4.552 -4.054 -27.333 1.00 20.00 B C
ATOM 6828 CG ASP H 486 5.885 -3.576 -26.790 1.00 20.00 B C
ATOM 6829 OD1 ASP H 486 6.284 -2.437 -27.115 1.00 20.00 B O
ATOM 6830 OD2 ASP H 486 6.556 -4.355 -26.080 1.00 20.00 B O
ATOM 6831 C ASP H 486 2.628 -3.456 -28.818 1.00 45.66 B C
ATOM 6832 O ASP H 486 2.683 -3.252 -30.034 1.00 39.86 B O
ATOM 6833 N GLU H 487 1.627 -4.107 -28.238 1.00 49.20 B N
ATOM 6834 CA GLU H 487 0.525 -4.652 -29.013 1.00 45.70 B C
ATOM 6835 CB GLU H 487 -0.444 -5.410 -28.105 1.00 20.00 B C
ATOM 6836 CG GLU H 487 0.156 -6.664 -27.483 1.00 20.00 B C
ATOM 6837 CD GLU H 487 -0.814 -7.393 -26.576 1.00 20.00 B C
ATOM 6838 OE1 GLU H 487 -1.852 -6.804 -26.214 1.00 20.00 B O
ATOM 6839 OE2 GLU H 487 -0.514 -8.540 -26.183 1.00 20.00 B O
ATOM 6840 C GLU H 487 -0.203 -3.556 -29.783 1.00 41.48 B C
ATOM 6841 O GLU H 487 -0.411 -3.674 -30.989 1.00 48.92 B o
ATOM 6842 N PHE H 488 -0.486 -2.447 -29.110 1.00 42.16 B N
ATOM 6843 CA PHE H 488 -1.183 -1.339 -29.747 1.00 39.33 B C
ATOM 6844 CB PHE H 488 -1.438 -0.219 -28.745 1.00 20.00 B c
ATOM 6845 CG PHE H 488 -2.369 -0.602 -27.638 1.00 20.00 B c
ATOM 6846 CD1 PHE H 488 -3.739 -0.595 -27.833 1.00 20.00 B c
ATOM 6847 CE1 PHE H 488 -4.602 -0.873 -26.789 1.00 20.00 B c
ATOM 6848 CZ PHE H 488 -4.095 -1.193 -25.546 1.00 20.00 B c
ATOM 6849 CE2 PHE H 488 -2.731 -1.192 -25.340 1.00 20.00 B c
ATOM 6850 CD2 PHE H 488 -1.876 -0.912 -26.385 1.00 20.00 B c
ATOM 6851 C PHE H 488 -0.401 -0.804 -30.939 1.00 43.06 B c
ATOM 6852 O PHE H 488 -0.977 -0.505 -31.984 1.00 61.71 B o
ATOM 6853 N ASP H 489 0.915 -0.700 -30.782 1.00 41.95 B N
ATOM 6854 CA ASP H 489 1.766 -0.104 -31.808 1.00 42.75 B c
ATOM 6855 CB ASP H 489 3.172 0.134 -31.262 1.00 20.00 B c
ATOM 6856 CG ASP H 489 3.235 1.317 -30.327 1.00 20.00 B c
ATOM 6857 OD1 ASP H 489 2.256 2.089 -30.288 1.00 20.00 B o
ATOM 6858 OD2 ASP H 489 4.252 1.462 -29.617 1.00 20.00 B o
ATOM 6859 C ASP H 489 1.837 -0.980 -33.054 1.00 45.61 B c
ATOM 6860 O ASP H 489 2.110 -0.495 -34.154 1.00 54.39 B o
ATOM 6861 N ALA H 490 1.702 -2.287 -32.853 1.00 42.89 B N
ATOM 6862 CA ALA H 490 1.705 -3.238 -33.957 1.00 38.40 B c
ATOM 6863 CB ALA H 490 1.928 -4.653 -33.436 1.00 20.00 B c
ATOM 6864 C ALA H 490 0.413 -3.160 -34.770 1.00 39.67 B c
ATOM 6865 O ALA H 490 0.443 -3.194 -35.998 1.00 56.80 B o
ATOM 6866 N SER H 491 -0.717 -3.050 -34.080 1.00 40.38 B N
ATOM 6867 CA SER H 491 -2.003 -2.833 -34.737 1.00 41.77 B c
ATOM 6868 CB SER H 491 -3.155 -2.963 -33.731 1.00 20.00 B c
ATOM 6869 OG SER H 491 -3.173 -1.878 -32.817 1.00 20.00 B o
ATOM 6870 C SER H 491 -2.056 -1.474 -35.432 1.00 39.01 B c
ATOM 6871 O SER H 491 -2.701 -1.325 -36.472 1.00 36.91 B o
ATOM 6872 N ILE H 492 -1.440 -0.470 -34.812 1.00 38.11 B N
ATOM 6873 CA ILE H 492 -1.342 0.863 -35.402 1.00 41.21 B c
ATOM 6874 CB ILE H 492 -0.651 1.856 -34.446 1.00 20.00 B c
ATOM 6875 CGI ILE H 492 -1.506 2.097 -33.203 1.00 20.00 B c
ATOM 6876 CD1 ILE H 492 -0.883 3.081 -32.232 1.00 20.00 B c
ATOM 6877 CG2 ILE H 492 -0.363 3.173 -35.150 1.00 20.00 B c
ATOM 6878 C ILE H 492 -0.561 0.826 -36.714 1.00 39.22 B C
ATOM 6879 O ILE H 492 -0.943 1.466 -37.696 1.00 47.54 B O
ATOM 6880 N SER H 493 0.535 0.073 -36.718 1.00 41.64 B N
ATOM 6881 CA SER H 493 1.307 -0.161 -37.933 1.00 35.15 B C ATOM 6882 CB SE H 493 2.587 -0.944 -37.618 1.00 20.00 B C
ATOM 6883 OG SER H 493 2.296 -2.250 -37.147 1.00 20.00 B o
ATOM 6884 C SER H 493 0.486 -0.880 -39.011 1.00 47.90 B c
ATOM 6885 O SER H 493 0.565 -0.538 -40.191 1.00 50.94 B o
ATOM 6886 N GLN H 494 -0.321 -1.855 -38.596 1.00 42.51 B N
ATOM 6887 CA GLN H 494 -1.175 -2.611 -39.517 1.00 41.96 B c
ATOM 6888 CB GLN H 494 -1.822 -3.801 -38.795 1.00 20.00 B c
ATOM 6889 CG GLN H 494 -0.843 -4.905 -38.423 1.00 20.00 B c
ATOM 6890 CD GLN H 494 -1.489 -6.019 -37.630 1.00 20.00 B c
ATOM 6891 OE1 GLN H 494 -2.536 -5.830 -37.011 1.00 20.00 B o
ATOM 6892 NE2 GLN H 494 -0.893 -7.205 -37.684 1.00 20.00 B N
ATOM 6893 C GLN H 494 -2.254 -1.721 -40.130 1.00 33.86 B c
ATOM 6894 O GLN H 494 -2.479 -1.743 -41.340 1.00 54.89 B o
ATOM 6895 N VAL H 495 -2.973 -1.005 -39.272 1.00 34.99 B N
ATOM 6896 CA VAL H 495 -3.955 -0.025 -39.718 1.00 38.42 B c
ATOM 6897 CB VAL H 495 -4.485 0.807 -38.536 1.00 20.00 B c
ATOM 6898 CGI VAL H 495 -5.501 1.828 -39.016 1.00 20.00 B c
ATOM 6899 CG2 VAL H 495 -5.088 -0.101 -37.479 1.00 20.00 B c
ATOM 6900 C VAL H 495 -3.344 0.912 -40.751 1.00 42.74 B c
ATOM 6901 O VAL H 495 -3.876 1.069 -41.850 1.00 44.00 B o
ATOM 6902 N ASN H 496 -2.171 1.447 -40.434 1.00 42.45 B N
ATOM 6903 CA ASN H 496 -1.500 2.382 -41.323 1.00 43.01 B c
ATOM 6904 CB ASN H 496 -0.202 2.880 -40.692 1.00 20.00 B c
ATOM 6905 CG ASN H 496 -0.446 3.770 -39.497 1.00 20.00 B c
ATOM 6906 OD1 ASN H 496 -1.517 4.360 -39.358 1.00 20.00 B o
ATOM 6907 ND2 ASN H 496 0.537 3.849 -38.608 1.00 20.00 B N
ATOM 6908 C ASN H 496 -1.227 1.780 -42.695 1.00 43.13 B c
ATOM 6909 O ASN H 496 -1.502 2.404 -43.720 1.00 54.76 B o
ATOM 6910 N GLU H 497 -0.737 0.544 -42.708 1.00 42.08 B N
ATOM 6911 CA GLU H 497 -0.453 -0.150 -43.957 1.00 43.13 B c
ATOM 6912 CB GLU H 497 0.151 -1.525 -43.678 1.00 20.00 B c
ATOM 6913 CG GLU H 497 1.651 -1.515 -43.476 1.00 20.00 B c
ATOM 6914 CD GLU H 497 2.193 -2.884 -43.108 1.00 20.00 B c
ATOM 6915 OE1 GLU H 497 1.402 -3.851 -43.058 1.00 20.00 B o
ATOM 6916 OE2 GLU H 497 3.419 -3.001 -42.899 1.00 20.00 B o
ATOM 6917 C GLU H 497 -1.724 -0.306 -44.781 1.00 49.77 B c
ATOM 6918 O GLU H 497 -1.680 -0.352 -46.011 1.00 42.88 B o
ATOM 6919 N LYS H 498 -2.846 -0.477 -44.088 1.00 41.82 B N
ATOM 6920 CA LYS H 498 -4.141 -0.621 -44.741 1.00 53.60 B c
ATOM 6921 CB LYS H 498 -5.174 -1.179 -43.761 1.00 20.00 B c
ATOM 6922 CG LYS H 498 -4.967 -2.641 -43.403 1.00 20.00 B c
ATOM 6923 CD LYS H 498 -6.078 -3.148 -42.491 1.00 20.00 B c
ATOM 6924 CE LYS H 498 -5.896 -4.624 -42.160 1.00 20.00 B c
ATOM 6925 NZ LYS H 498 -6.862 -5.090 -41.127 1.00 20.00 B N
ATOM 6926 C LYS H 498 -4.622 0.716 -45.298 1.00 55.29 B c
ATOM 6927 O LYS H 498 -5.273 0.766 -46.340 1.00 61.06 B o
ATOM 6928 N ILE H 499 -4.359 1.789 -44.558 1.00 52.22 B N
ATOM 6929 CA ILE H 499 -4.606 3.140 -45.052 1.00 48.26 B c
ATOM 6930 CB ILE H 499 -4.213 4.205 -44.012 1.00 20.00 B c
ATOM 6931 CGI ILE H 499 -5.137 4.139 -42.797 1.00 20.00 B c
ATOM 6932 CD1 ILE H 499 -4.719 5.058 -41.669 1.00 20.00 B c
ATOM 6933 CG2 ILE H 499 -4.246 5.594 -44.631 1.00 20.00 B c
ATOM 6934 C ILE H 499 -3.809 3.400 -46.323 1.00 49.07 B C
ATOM 6935 O ILE H 499 -4.273 4.090 -47.232 1.00 58.45 B O
ATOM 6936 N ASN H 500 -2.600 2.849 -46.371 1.00 51.02 B N
ATOM 6937 CA ASN H 500 -1.718 3.000 -47.524 1.00 52.06 B c
ATOM 6938 CB ASN H 500 -0.284 2.663 -47.120 1.00 20.00 B c
ATOM 6939 CG ASN H 500 0.707 2.898 -48.233 1.00 20.00 B c
ATOM 6940 OD1 ASN H 500 0.607 3.875 -48.973 1.00 20.00 B o
ATOM 6941 ND2 ASN H 500 1.740 2.071 -48.275 1.00 20.00 B N ATOM 6942 C ASN H 500 -2.151 2.149 -48.719 1.00 48.31 B C
ATOM 6943 O ASN H 500 -1.841 2.469 -49.867 1.00 56.89 B o
ATOM 6944 N GLN H 501 -2.872 1.067 -48.438 1.00 55.87 B N
ATOM 6945 CA GLN H 501 -3.511 0.269 -49.480 1.00 53.55 B C
ATOM 6946 CB GLN H 501 -3.879 -1.116 -48.940 1.00 20.00 B c
ATOM 6947 CG GLN H 501 -2.685 -1.963 -48.513 1.00 20.00 B c
ATOM 6948 CD GLN H 501 -3.093 -3.333 -47.996 1.00 20.00 B c
ATOM 6949 OE1 GLN H 501 -4.169 -3.495 -47.420 1.00 20.00 B o
ATOM 6950 NE2 GLN H 501 -2.215 -4.317 -48.162 1.00 20.00 B N
ATOM 6951 C GLN H 501 -4.755 0.964 -50.023 1.00 45.67 B c
ATOM 6952 O GLN H 501 -4.984 0.994 -51.232 1.00 58.31 B o
ATOM 6953 N SE H 502 -5.525 1.570 -49.124 1.00 43.44 B N
ATOM 6954 CA SE H 502 -6.702 2.345 -49.508 1.00 45.40 B c
ATOM 6955 CB SE H 502 -7.471 2.800 -48.264 1.00 20.00 B c
ATOM 6956 OG SE H 502 -6.684 3.664 -47.464 1.00 20.00 B o
ATOM 6957 C SER H 502 -6.319 3.555 -50.358 1.00 55.15 B c
ATOM 6958 O SER H 502 -7.049 3.943 -51.270 1.00 52.57 B o
ATOM 6959 N LEU H 503 -5.160 4.135 -50.060 1.00 55.35 B N
ATOM 6960 CA LEU H 503 -4.662 5.286 -50.805 1.00 52.12 B c
ATOM 6961 CB LEU H 503 -3.529 5.973 -50.037 1.00 20.00 B c
ATOM 6962 CG LEU H 503 -3.896 6.598 -48.688 1.00 20.00 B c
ATOM 6963 CD1 LEU H 503 -2.646 7.032 -47.948 1.00 20.00 B c
ATOM 6964 CD2 LEU H 503 -4.847 7.769 -48.868 1.00 20.00 B c
ATOM 6965 C LEU H 503 -4.187 4.882 -52.197 1.00 55.74 B c
ATOM 6966 O LEU H 503 -4.339 5.636 -53.159 1.00 57.75 B o
ATOM 6967 N ALA H 504 -3.608 3.691 -52.295 1.00 57.22 B N
ATOM 6968 CA ALA H 504 -3.204 3.150 -53.584 1.00 59.12 B c
ATOM 6969 CB ALA H 504 -2.319 1.930 -53.394 1.00 20.00 B c
ATOM 6970 C ALA H 504 -4.423 2.802 -54.427 1.00 58.10 B c
ATOM 6971 O ALA H 504 -4.488 3.145 -55.608 1.00 63.64 B o
ATOM 6972 N PHE H 505 -5.421 2.194 -53.793 1.00 58.17 B N
ATOM 6973 CA PHE H 505 -6.683 1.909 -54.464 1.00 56.56 B c
ATOM 6974 CB PHE H 505 -7.657 1.198 -53.517 1.00 20.00 B c
ATOM 6975 CG PHE H 505 -7.174 -0.142 -53.045 1.00 20.00 B c
ATOM 6976 CD1 PHE H 505 -7.297 -1.263 -53.851 1.00 20.00 B c
ATOM 6977 CE1 PHE H 505 -6.817 -2.490 -53.432 1.00 20.00 B c
ATOM 6978 CZ PHE H 505 -6.236 -2.610 -52.183 1.00 20.00 B c
ATOM 6979 CE2 PHE H 505 -6.106 -1.497 -51.373 1.00 20.00 B c
ATOM 6980 CD2 PHE H 505 -6.566 -0.272 -51.809 1.00 20.00 B c
ATOM 6981 C PHE H 505 -7.307 3.189 -55.020 1.00 60.12 B c
ATOM 6982 O PHE H 505 -7.761 3.223 -56.166 1.00 65.46 B o
ATOM 6983 N ILE H 506 -7.214 4.267 -54.247 1.00 56.10 B N
ATOM 6984 CA ILE H 506 -7.762 5.552 -54.667 1.00 57.32 B c
ATOM 6985 CB ILE H 506 -7.716 6.599 -53.536 1.00 20.00 B c
ATOM 6986 CGI ILE H 506 -8.610 6.163 -52.376 1.00 20.00 B c
ATOM 6987 CD1 ILE H 506 -8.728 7.191 -51.274 1.00 20.00 B c
ATOM 6988 CG2 ILE H 506 -8.177 7.956 -54.049 1.00 20.00 B c
ATOM 6989 C ILE H 506 -7.013 6.084 -55.883 1.00 67.33 B C
ATOM 6990 O ILE H 506 -7.625 6.563 -56.839 1.00 76.99 B 1 □
ATOM 6991 N ARG H 507 -5.694 5.913 -55.876 1.00 67.87 B N
ATOM 6992 CA ARG H 507 -4.858 6.338 -56.993 1.00 62.11 B c
ATOM 6993 CB ARG H 507 -3.381 6.153 -56.657 1.00 20.00 B c
ATOM 6994 CG ARG H 507 -2.862 7.130 -55.630 1.00 20.00 B c
ATOM 6995 CD ARG H 507 -1.380 6.930 -55.386 1.00 20.00 B c
ATOM 6996 NE ARG H 507 -0.903 7.783 -54.303 1.00 20.00 B N
ATOM 6997 CZ ARG H 507 0.322 7.729 -53.792 1.00 20.00 B c
ATOM 6998 NH1 ARG H 507 1.215 6.883 -54.288 1.00 20.00 B N
ATOM 6999 NH2 ARG H 507 0.656 8.530 -52.791 1.00 20.00 B N
ATOM 7000 C ARG H 507 -5.191 5.565 -58.258 1.00 67.30 B C
ATOM 7001 O ARG H 507 -5.255 6.139 -59.344 1.00 67.02 B o ATOM 7002 N LYS H 508 -5.222 4.243 -58.139 1.00 66.83 B N
ATOM 7003 CA LYS H 508 -5.694 3.391 -59.220 1.00 68.12 B C
ATOM 7004 CB LYS H 508 -5.743 1.932 -58.763 1.00 20.00 B C
ATOM 7005 CG LYS H 508 -4.368 1.325 -58.543 1.00 20.00 B c
ATOM 7006 CD LYS H 508 -4.433 -0.159 -58.230 1.00 20.00 B c
ATOM 7007 CE LYS H 508 -3.037 -0.710 -57.973 1.00 20.00 B c
ATOM 7008 NZ LYS H 508 -3.053 -2.129 -57.525 1.00 20.00 B N
ATOM 7009 C LYS H 508 -7.065 3.839 -59.705 1.00 65.22 B c
ATOM 7010 O LYS H 508 -7.245 4.154 -60.881 1.00 72.34 B o
ATOM 7011 N SE H 509 -7.996 3.977 -58.767 1.00 64.87 B N
ATOM 7012 CA SE H 509 -9.366 4.349 -59.095 1.00 56.47 B c
ATOM 7013 CB SE H 509 -10.227 4.420 -57.832 1.00 20.00 B c
ATOM 7014 OG SE H 509 -9.862 5.523 -57.023 1.00 20.00 B o
ATOM 7015 C SER H 509 -9.418 5.673 -59.851 1.00 56.96 B c
ATOM 7016 O SER H 509 -10.124 5.796 -60.854 1.00 65.57 B o
ATOM 7017 N ASP H 510 -8.670 6.661 -59.368 1.00 64.34 B N
ATOM 7018 CA ASP H 510 -8.624 7.971 -60.009 1.00 64.83 B c
ATOM 7019 CB ASP H 510 -7.774 8.944 -59.192 1.00 20.00 B c
ATOM 7020 CG ASP H 510 -8.421 9.315 -57.872 1.00 20.00 B c
ATOM 7021 OD1 ASP H 510 -9.589 8.927 -57.652 1.00 20.00 B o
ATOM 7022 OD2 ASP H 510 -7.729 9.904 -57.015 1.00 20.00 B o
ATOM 7023 C ASP H 510 -8.087 7.873 -61.431 1.00 62.11 B c
ATOM 7024 O ASP H 510 -8.711 8.358 -62.373 1.00 67.61 B o
ATOM 7025 N GLU H 511 -6.939 7.222 -61.584 1.00 64.95 B N
ATOM 7026 CA GLU H 511 -6.330 7.042 -62.896 1.00 60.64 B c
ATOM 7027 CB GLU H 511 -5.117 6.109 -62.804 1.00 20.00 B c
ATOM 7028 CG GLU H 511 -3.959 6.673 -61.982 1.00 20.00 B c
ATOM 7029 CD GLU H 511 -2.858 5.655 -61.716 1.00 20.00 B c
ATOM 7030 OE1 GLU H 511 -3.140 4.438 -61.756 1.00 20.00 B o
ATOM 7031 OE2 GLU H 511 -1.749 6.076 -61.324 1.00 20.00 B o
ATOM 7032 C GLU H 511 -7.340 6.528 -63.928 1.00 59.91 B c
ATOM 7033 O GLU H 511 -7.417 7.043 -65.045 1.00 55.45 B o
ATOM 7034 N LEU H 512 -8.137 5.537 -63.533 1.00 44.35 B N
ATOM 7035 CA LEU H 512 -9.117 4.929 -64.432 1.00 49.60 B c
ATOM 7036 CB LEU H 512 -9.744 3.682 -63.796 1.00 20.00 B c
ATOM 7037 CG LEU H 512 -8.841 2.462 -63.572 1.00 20.00 B c
ATOM 7038 CD1 LEU H 512 -9.594 1.368 -62.825 1.00 20.00 B c
ATOM 7039 CD2 LEU H 512 -8.295 1.930 -64.892 1.00 20.00 B c
ATOM 7040 C LEU H 512 -10.208 5.920 -64.821 1.00 58.00 B c
ATOM 7041 O LEU H 512 -10.524 6.073 -66.000 1.00 55.11 B o
ATOM 7042 N LEU H 513 -10.814 6.552 -63.820 1.00 57.91 B N
ATOM 7043 CA LEU H 513 -11.866 7.536 -64.057 1.00 57.49 B c
ATOM 7044 CB LEU H 513 -12.390 8.097 -62.733 1.00 20.00 B c
ATOM 7045 CG LEU H 513 -13.077 7.088 -61.815 1.00 20.00 B c
ATOM 7046 CD1 LEU H 513 -13.388 7.705 -60.461 1.00 20.00 B , c
ATOM 7047 CD2 LEU H 513 -14.336 6.556 -62.474 1.00 20.00 B , c
ATOM 7048 C LEU H 513 -11.384 8.676 -64.949 1.00 58.78 B c
ATOM 7049 O LEU H 513 -12.154 9.220 -65.740 1.00 59.88 B o
ATOM 7050 N HIS H 514 -10.131 9.086 -64.764 1.00 60.07 B N
ATOM 7051 CA HIS H 514 -9.544 10.151 -65.578 1.00 62.82 B c
ATOM 7052 CB HIS H 514 -8.240 10.665 -64.951 1.00 20.00 B c
ATOM 7053 CG HIS H 514 -8.406 11.218 -63.567 1.00 20.00 B c
ATOM 7054 ND1 HIS H 514 -9.083 12.390 -63.308 1.00 20.00 B N
ATOM 7055 CE1 HIS H 514 -9.060 12.634 -62.010 1.00 20.00 B c
ATOM 7056 NE2 HIS H 514 -8.393 11.660 -61.416 1.00 20.00 B N
ATOM 7057 CD2 HIS H 514 -7.960 10.770 -62.368 1.00 20.00 B C
ATOM 7058 C HIS H 514 -9.305 9.679 -67.014 1.00 65.10 B C
ATOM 7059 O HIS H 514 -9.352 10.475 -67.953 1.00 66.73 B o
ATOM 7060 N ASN H 515 -9.179 8.365 -67.187 1.00 63.45 B N
ATOM 7061 CA ASN H 515 -9.028 7.768 -68.513 1.00 56.53 B C ATOM 7062 CB ASN H 515 -8.367 6.392 -68.409 1.00 20.00 B C
ATOM 7063 CG ASN H 515 -6.901 6.476 -68.035 1.00 20.00 B C
ATOM 7064 OD1 ASN H 515 -6.233 7.470 -68.319 1.00 20.00 B o
ATOM 7065 ND2 ASN H 515 -6.375 5.399 -67.462 1.00 20.00 B N
ATOM 7066 C ASN H 515 -10.357 7.651 -69.254 1.00 60.06 B C
ATOM 7067 O ASN H 515 -10.414 7.816 -70.473 1.00 66.48 B o
ATOM 7068 N VAL H 516 -11.402 7.275 -68.522 1.00 54.29 B N
ATOM 7069 CA VAL H 516 -12.765 7.256 -69.056 1.00 52.70 B C
ATOM 7070 CB VAL H 516 -13.775 6.751 -68.001 1.00 20.00 B c
ATOM 7071 CGI VAL H 516 -15.194 6.825 -68.541 1.00 20.00 B c
ATOM 7072 CG2 VAL H 516 -13.431 5.333 -67.568 1.00 20.00 B c
ATOM 7073 C VAL H 516 -13.206 8.633 -69.557 1.00 60.10 B c
ATOM 7074 O VAL H 516 -13.761 8.759 -70.649 1.00 61.55 B o
ATOM 7075 N ASN H 517 -12.957 9.661 -68.752 1.00 69.10 B N
ATOM 7076 CA ASN H 517 -13.297 11.030 -69.125 1.00 67.75 B c
ATOM 7077 CB ASN H 517 -12.850 12.012 -68.038 1.00 20.00 B c
ATOM 7078 CG ASN H 517 -13.685 11.907 -66.774 1.00 20.00 B c
ATOM 7079 OD1 ASN H 517 -14.835 11.471 -66.813 1.00 20.00 B , o
ATOM 7080 ND2 ASN H 517 -13.126 12.355 -65.653 1.00 20.00 B , N
ATOM 7081 C ASN H 517 -12.686 11.424 -70.465 1.00 71.17 B c
ATOM 7082 O ASN H 517 -13.289 12.169 -71.238 1.00 66.42 B o
ATOM 7083 N ALA H 518 -11.489 10.912 -70.739 1.00 72.11 B N
ATOM 7084 CA ALA H 518 -10.794 11.202 -71.989 1.00 74.82 B c
ATOM 7085 CB ALA H 518 -9.318 10.855 -71.867 1.00 20.00 B c
ATOM 7086 C ALA H 518 -11.421 10.450 -73.155 1.00 70.11 B c
ATOM 7087 O ALA H 518 -11.593 11.001 -74.242 1.00 65.18 B o
ATOM 7088 N GLY H 519 -11.665 9.160 -72.952 1.00 56.07 B N
ATOM 7089 CA GLY H 519 -12.395 8.360 -73.926 1.00 53.01 B c
ATOM 7090 C GLY H 519 -13.763 8.941 -74.222 1.00 63.58 B c
ATOM 7091 O GLY H 519 -14.203 8.960 -75.371 1.00 69.35 B o
ATOM 7092 N LYS H 520 -14.422 9.444 -73.183 1.00 58.33 B N
ATOM 7093 CA LYS H 520 -15.716 10.101 -73.333 1.00 53.44 B c
ATOM 7094 CB LYS H 520 -16.241 10.557 -71.975 1.00 20.00 B c
ATOM 7095 CG LYS H 520 -16.441 9.429 -70.996 1.00 20.00 B c
ATOM 7096 CD LYS H 520 -16.739 9.961 -69.616 1.00 20.00 B c
ATOM 7097 CE LYS H 520 -17.296 8.868 -68.730 1.00 20.00 B c
ATOM 7098 NZ LYS H 520 -17.807 9.424 -67.452 1.00 20.00 B N
ATOM 7099 C LYS H 520 -15.623 11.296 -74.268 1.00 58.24 B c
ATOM 7100 O LYS H 520 -16.579 11.621 -74.972 1.00 48.60 B o
ATOM 7101 N SE H 521 -14.489 11.986 -74.219 1.00 67.19 B N
ATOM 7102 CA SER H 521 -14.232 13.101 -75.120 1.00 60.42 B c
ATOM 7103 CB SER H 521 -12.938 13.821 -74.727 1.00 20.00 B c
ATOM 7104 OG SER H 521 -11.894 12.898 -74.459 1.00 20.00 B o
ATOM 7105 C SER H 521 -14.167 12.636 -76.573 1.00 54.19 B c
ATOM 7106 O SER H 521 -14.886 13.151 -77.430 1.00 65.36 B o
ATOM 7107 N THR H 522 -13.362 11.609 -76.825 1.00 50.09 B N
ATOM 7108 CA THR H 522 -13.259 11.025 -78.158 1.00 57.59 B c
ATOM 7109 CB THR H 522 -12.299 9.817 -78.179 1.00 20.00 B c
ATOM 7110 OG1 THR H 522 -12.774 8.810 -77.278 1.00 20.00 B o
ATOM 7111 CG2 THR H 522 -10.894 10.235 -77.767 1.00 20.00 B c
ATOM 7112 C THR H 522 -14.625 10.565 -78.646 1.00 59.16 B c
ATOM 7113 O THR H 522 -15.044 10.893 -79.755 1.00 65.90 B o
ATOM 7114 N THR H 523 -15.338 9.849 -77.783 1.00 52.59 B N
ATOM 7115 CA THR H 523 -16.665 9.347 -78.112 1.00 42.19 B c
ATOM 7116 CB THR H 523 -17.298 8.599 -76.922 1.00 20.00 B c
ATOM 7117 OG1 THR H 523 -17.543 9.516 -75.848 1.00 20.00 B o
ATOM 7118 CG2 THR H 523 -16.373 7.492 -76.435 1.00 20.00 B c
ATOM 7119 C THR H 523 -17.596 10.466 -78.566 1.00 48.90 B c
ATOM 7120 O THR H 523 -18.331 10.314 -79.541 1.00 63.19 B o
ATOM 7121 N ASN H 524 -17.535 11.601 -77.881 1.00 52.51 B N ATOM 7122 CA ASN H 524 -18.341 12.752 -78.258 1.00 57.54 B C
ATOM 7123 CB ASN H 524 -18.235 13.853 -77.202 1.00 20.00 B C
ATOM 7124 CG ASN H 524 -19.015 13.528 -75.945 1.00 20.00 B C
ATOM 7125 OD1 ASN H 524 -19.910 12.682 -75.959 1.00 20.00 B O
ATOM 7126 ND2 ASN H 524 -18.683 14.203 -74.850 1.00 20.00 B N
ATOM 7127 C ASN H 524 -17.956 13.287 -79.633 1.00 54.12 B C
ATOM 7128 O ASN H 524 -18.812 13.463 -80.500 1.00 61.31 B O
ATOM 7129 N SE H 525 -16.656 13.422 -79.866 1.00 48.97 B N
ATOM 7130 CA SER H 525 -16.165 13.913 -81.145 1.00 64.81 B C
ATOM 7131 CB SER H 525 -14.636 13.940 -81.151 1.00 61.22 B C
ATOM 7132 OG SER H 525 -14.141 14.856 -80.191 1.00 85.90 B O
ATOM 7133 C SER H 525 -16.689 13.053 -82.292 1.00 69.67 B C
ATOM 7134 O SER H 525 -17.013 13.563 -83.367 1.00 72.60 B O
ATOM 7135 N LYS H 526 -16.849 11.760 -82.029 1.00 66.06 B N
ATOM 7136 CA LYS H 526 -17.335 10.831 -83.043 1.00 63.67 B C
ATOM 7137 CB LYS H 526 -17.003 9.383 -82.660 1.00 70.55 B C
ATOM 7138 CG LYS H 526 -15.562 8.963 -82.939 1.00 75.29 B C
ATOM 7139 CD LYS H 526 -15.205 7.681 -82.194 1.00 85.03 B C
ATOM 7140 CE LYS H 526 -13.700 7.525 -82.041 1.00 82.65 B C
ATOM 7141 NZ LYS H 526 -13.347 6.537 -80.984 1.00 73.89 B N
ATOM 7142 C LYS H 526 -18.838 10.987 -83.239 1.00 55.36 B C
ATOM 7143 O LYS H 526 -19.333 10.950 -84.365 1.00 70.69 B O
ATOM 7144 N ILE H 527 -19.560 11.149 -82.135 1.00 57.52 B N
ATOM 7145 CA ILE H 527 -20.995 11.389 -82.189 1.00 58.48 B C
ATOM 7146 CB ILE H 527 -21.569 11.642 -80.787 1.00 57.00 B C
ATOM 7147 CGI ILE H 527 -21.356 10.420 -79.891 1.00 49.07 B C
ATOM 7148 CD1 ILE H 527 -21.790 9.118 -80.517 1.00 46.18 B C
ATOM 7149 CG2 ILE H 527 -23.035 12.029 -80.872 1.00 52.63 B C
ATOM 7150 C ILE H 527 -21.317 12.586 -83.075 1.00 65.20 B C
ATOM 7151 O ILE H 527 -22.228 12.532 -83.900 1.00 66.48 B O
ATOM 7152 N TYR H 528 -20.590 13.681 -82.870 1.00 69.78 B N
ATOM 7153 CA TYR H 528 -20.780 14.884 -83.673 1.00 72.52 B C
ATOM 7154 CB TYR H 528 -19.738 15.948 -83.316 1.00 73.16 B C
ATOM 7155 CG TYR H 528 -19.707 16.343 -81.856 1.00 76.94 B C
ATOM 7156 CD1 TYR H 528 -18.615 17.018 -81.327 1.00 70.95 B C
ATOM 7157 CE1 TYR H 528 -18.584 17.406 -80.000 1.00 67.73 B C
ATOM 7158 CZ TYR H 528 -19.653 17.114 -79.180 1.00 71.89 B C
ATOM 7159 OH TYR H 528 -19.626 17.490 -77.856 1.00 75.44 B O
ATOM 7160 CE2 TYR H 528 -20.759 16.464 -79.687 1.00 77.03 B C
ATOM 7161 CD2 TYR H 528 -20.782 16.084 -81.018 1.00 77.84 B C
ATOM 7162 C TYR H 528 -20.678 14.551 -85.157 1.00 71.63 B C
ATOM 7163 O TYR H 528 -21.609 14.797 -85.925 1.00 84.20 B O
ATOM 7164 N HIS H 529 -19.526 14.025 -85.559 1.00 67.69 B N
ATOM 7165 CA HIS H 529 -19.265 13.733 -86.962 1.00 60.28 B C
ATOM 7166 CB HIS H 529 -17.883 13.102 -87.131 1.00 67.84 B C
ATOM 7167 CG HIS H 529 -16.752 14.042 -86.853 1.00 88.54 B C
ATOM 7168 ND1 HIS H 529 -15.514 13.914 -87.444 1.00 93.34 B N
ATOM 7169 CE1 HIS H 529 -14.718 14.874 -87.007 1.00 86.23 B C
ATOM 7170 NE2 HIS H 529 -15.394 15.614 -86.145 1.00 91.95 B N
ATOM 7171 CD2 HIS H 529 -16.667 15.110 -86.026 1.00 93.77 B C
ATOM 7172 C HIS H 529 -20.333 12.817 -87.546 1.00 63.30 B C
ATOM 7173 O HIS H 529 -20.803 13.034 -88.663 1.00 61.02 B O
ATOM 7174 N ILE H 530 -20.710 11.791 -86.791 1.00 59.79 B N
ATOM 7175 CA ILE H 530 -21.800 10.915 -87.201 1.00 45.70 B C
ATOM 7176 CB ILE H 530 -22.019 9.780 -86.190 1.00 40.57 B C
ATOM 7177 CGI ILE H 530 -20.879 8.765 -86.292 1.00 42.86 B C
ATOM 7178 CD1 ILE H 530 -20.826 7.775 -85.154 1.00 51.01 B C
ATOM 7179 CG2 ILE H 530 -23.360 9.108 -86.437 1.00 35.31 B C
ATOM 7180 C ILE H 530 -23.085 11.717 -87.331 1.00 57.52 B C
ATOM 7181 O ILE H 530 -23.779 11.645 -88.345 1.00 71.18 B O ATOM 7182 N GLU H 531 -23.322 12.569 -86.341 1.00 67.55 B N
ATOM 7183 CA GLU H 531 -24.479 13.449 86.325 1.00 69.79 B C
ATOM 7184 CB GLU H 531 -24.440 14.327 85.074 1.00 84.02 B C
ATOM 7185 CG GLU H 531 -25.803 14.718 84.541 1.00104.22 B c
ATOM 7186 CD GLU H 531 -25.706 15.531 83.270 1.00116.08 B c
ATOM 7187 OE1 GLU H 531 -25.017 15.079 -82.331 1.00118.71 B o
ATOM 7188 OE2 GLU H 531 -26.222 16.669 -83.251 1.00119.69 B o
ATOM 7189 C GLU H 531 -24.506 14.328 87.569 1.00 64.87 B c
ATOM 7190 O GLU H 531 -25.517 14.404 88.269 1.00 55.58 B o
ATOM 7191 N ASN H 532 -23.394 15.011 -87.821 1.00 65.70 B N
ATOM 7192 CA ASN H 532 -23.273 15.890 -88.979 1.00 64.16 B c
ATOM 7193 CB ASN H 532 -21.931 16.625 -88.953 1.00 60.58 B c
ATOM 7194 CG ASN H 532 -21.793 17.621 -90.085 1.00 67.75 B c
ATOM 7195 OD1 ASN H 532 -22.591 18.550 -90.206 1.00 53.59 B o
ATOM 7196 ND2 ASN H 532 -20.822 17.392 -90.961 1.00 61.81 B N
ATOM 7197 C ASN H 532 -23.418 15.119 -90.284 1.00 72.17 B c
ATOM 7198 O ASN H 532 -24.041 15.593 -91.233 1.00 85.75 B o
ATOM 7199 N GLU H 533 -22.870 13.909 -90.300 1.00 79.68 B N
ATOM 7200 CA GLU H 533 -22.922 13.044 -91.468 1.00 71.96 B c
ATOM 7201 CB GLU H 533 -22.010 11.837 -91.264 1.00 67.87 B c
ATOM 7202 CG GLU H 533 -21.638 11.131 -92.547 1.00 81.94 B c
ATOM 7203 CD GLU H 533 -20.906 12.037 -93.515 1.00 92.79 B c
ATOM 7204 OE1 GLU H 533 -19.930 12.692 -93.094 1.00 95.90 B o
ATOM 7205 OE2 GLU H 533 -21.247 12.025 -94.716 1.00 93.14 B o
ATOM 7206 C GLU H 533 -24.342 12.570 -91.747 1.00 68.54 B c
ATOM 7207 O GLU H 533 -24.667 12.175 -92.866 1.00 79.29 B o
ATOM 7208 N ILE H 534 25.137 12.470 -90.688 1.00 69.50 B
ATOM 7209 CA ILE H 534 -26.529 12.076 -90.817 1.00 72.55 B c
ATOM 7210 CB ILE H 534 -27.056 11.467 -89.514 1.00 79.55 B c
ATOM 7211 CGI ILE H 534 -26.263 10.209 -89.164 1.00 80.41 B c
ATOM 7212 CD1 ILE H 534 -25.562 9.592 -90.348 1.00 89.38 B c
ATOM 7213 CG2 ILE H 534 -28.526 11.138 -89.645 1.00 78.63 B c
ATOM 7214 C ILE H 534 - 27.389 13.273 -91.189 1.00 74.92 B c
ATOM 7215 O ILE H 534 28.479 13.120 -91.740 1.00 81.01 B o
ATOM 7216 N ALA H 535 -26.880 14.465 -90.903 1.00 79.52 B N
ATOM 7217 CA ALA H 535 -27.559 15.690 -91.290 1.00 82.64 B c
ATOM 7218 CB ALA H 535 -27.016 16.867 -90.498 1.00 75.39 B c
ATOM 7219 C ALA H 535 -27.440 15.939 -92.795 1.00 81.39 B c
ATOM 7220 O ALA H 535 -28.408 16.341 -93.443 1.00 85.54 B o
ATOM 7221 N A G H 536 -26.274 15.630 -93.358 1.00 78.41 B N
ATOM 7222 CA ARG H 536 -26.044 15.812 -94.791 1.00 83.27 B c
ATOM 7223 CB ARG H 536 -24.545 15.814 -95.106 1.00 84.58 B c
ATOM 7224 CG ARG H 536 -23.776 16.993 -94.527 1.00103.24 B c
ATOM 7225 CD ARG H 536 -22.638 17.422 -95.449 1.00114.72 B c
ATOM 7226 NE ARG H 536 -21.692 16.343 -95.722 1.00117.80 B N
ATOM 7227 CZ ARG H 536 -20.692 16.430 -96.594 1.00116.66 B c
ATOM 7228 NH1 ARG H 536 -20.522 17.538 -97.303 1.00114.57 B N
ATOM 7229 NH2 ARG H 536 -19.885 15.396 -96.786 1.00116.38 B N
ATOM 7230 C ARG H 536 -26.744 14.727 -95.606 1.00 82.20 B C
ATOM 7231 O ARG H 536 -27.369 15.011 -96.627 1.00 86.28 B O
ATOM 7232 N ILE H 537 26.598 13.479 -95.172 1.00 77.08 B N
ATOM 7233 CA ILE H 537 -27.315 12.371 -95.782 1.00 66.79 B C
ATOM 7234 CB ILE H 537 -26.955 11.038 -95.113 1.00 64.76 B C
ATOM 7235 CGI ILE H 537 -25.523 10.627 -95.476 1.00 66.92 B C
ATOM 7236 CD1 ILE H 537 -24.906 9.625 -94.519 1.00 70.83 B C
ATOM 7237 CG2 ILE H 537 -27.960 9.964 -95.497 1.00 51.02 B C
ATOM 7238 C ILE H 537 - 28.817 12.585 -95.674 1.00 74.94 B C
ATOM 7239 O ILE H 537 29.587 12.070 -96.482 1.00 97.16 B O
ATOM 7240 N LYS H 538 -29.232 13.337 -94.661 1.00 75.09 B N
ATOM 7241 CA LYS H 538 -30.640 13.666 -94.485 1.00 90.28 B C ATOM 7242 CB LYS H 538 -30.958 13.868 -93.003 1.00 93.73 B C
ATOM 7243 CG LYS H 538 -32.344 13.390 -92.575 1.00 96.60 B C
ATOM 7244 CD LYS H 538 -32.640 13.787 -91.126 1.00 95.37 B C
ATOM 7245 CE LYS H 538 -34.127 13.714 -90.798 1.00100.63 B C
ATOM 7246 NZ LYS H 538 -34.398 14.067 -89.375 1.00 99.58 B N
ATOM 7247 C LYS H 538 -31.022 14.911 -95.284 1.00102.20 B C
ATOM 7248 O LYS H 538 -32.166 15.360 -95.235 1.00112.11 B O
ATOM 7249 N LYS H 539 -30.069 15.444 -96.043 1.00105.15 B N
ATOM 7250 CA LYS H 539 -30.317 16.603 -96.899 1.00105.65 B C
ATOM 7251 CB LYS H 539 -29.144 17.589 -96.823 1.00110.12 B C
ATOM 7252 CG LYS H 539 -29.408 18.944 -97.481 1.00113.31 B C
ATOM 7253 CD LYS H 539 -28.182 19.854 -97.435 1.00114.26 B C
ATOM 7254 CE LYS H 539 -28.426 21.145 -98.205 1.00118.39 B C
ATOM 7255 NZ LYS H 539 -27.168 21.897 -98.470 1.00121.77 B N
ATOM 7256 C LYS H 539 -30.572 16.187 -98.347 1.00108.88 B C
ATOM 7257 O LYS H 539 -30.886 17.021 -99.195 1.00110.77 B O
ATOM 7258 N LEU H 540 -30.515 14.884 -98.605 1.00111.50 B N
ATOM 7259 CA LEU H 540 -30.796 14.356 -99.935 1.00110.31 B C
ATOM 7260 CB LEU H 540 -29.690 13.389-100.368 1.00101.19 B C
ATOM 7261 CG LEU H 540 -28.270 13.889-100.078 1.00 94.26 B C
ATOM 7262 CD 1 LEU H 540 -27.249 12.769-100.179 1.00 86.40 B C
ATOM 7263 CD2 LEU H 540 -27.896 15.059-100.984 1.00 84.54 B C
ATOM 7264 C LEU H 540 -32.157 13.675 -99.961 1.00118.37 B C
ATOM 7265 O LEU H 540 -32.531 13.039-100.945 1.00116.71 B O
ATOM 7266 N ILE H 541 -32.923 13.883 -98.896 1.00130.80 B N
ATOM 7267 CA ILE H 541 -34.267 13.339 -98.801 1.00140.48 B C
ATOM 7268 CB ILE H 541 -34.250 11.862 -98.372 1.00138.99 B C
ATOM 7269 CGI ILE H 541 -33.319 11.059 -99.282 1.00133.30 B C
ATOM 7270 CD 1 ILE H 541 -33.895 10.789-100.656 1.00136.26 B C
ATOM 7271 CG2 ILE H 541 -35.653 11.281 -98.432 1.00136.12 B C
ATOM 7272 C ILE H 541 -35.146 14.139 -97.839 1.00144.97 B C
ATOM 7273 O ILE H 541 -36.372 14.063 -97.905 1.00145.83 B O
ATOM 7274 N GLY H 542 -34.523 14.940 -96.979 1.00148.77 B N
ATOM 7275 CA GLY H 542 -35.267 15.725 -95.991 1.00153.58 B C
ATOM 7276 C GLY H 542 -35.358 17.210 -96.308 1.00160.45 B C
ATOM 7277 O GLY H 542 -35.594 17.599 -97.454 1.00163.41 B O
ATOM 7278 N GLU H 543 -35.275 18.034 -95.267 1.00163.83 B N
ATOM 7279 CA GLU H 543 -35.152 19.480 -95.430 1.00165.52 B C
ATOM 7280 CB GLU H 543 -35.727 20.205 -94.211 1.00158.94 B C
ATOM 7285 C GLU H 543 -33.698 19.890 -95.644 1.00168.27 B C
ATOM 7286 O GLU H 543 -32.778 19.116 -95.373 1.00167.37 B O
ATOM 7287 N GLN I 26 21.181 -26.937 -9.836 1.00 23.62 C N
ATOM 7288 CA GLN I 26 21.159 -25.618 -10.530 1.00 23.82 C C
ATOM 7289 CB GLN I 26 21.607 -24.503 -9.580 1.00 23.94 C C
ATOM 7290 CG GLN I 26 20.888 -24.492 -8.237 1.00 28.83 C C
ATOM 7291 CD GLN I 26 21.323 -25.626 -7.329 1.00 36.36 C C
ATOM 7292 OE1 GLN I 26 20.813 -26.740 -7.428 1.00 39.09 C O
ATOM 7293 NE2 GLN I 26 22.207 -25.325 -6.384 1.00 37.86 C N
ATOM 7294 C GLN I 26 22.043 -25.641 -11.774 1.00 23.09 C C
ATOM 7295 O GLN I 26 22.946 -26.471 -11.888 1.00 24.21 C O
ATOM 7296 N ASN I 27 21.670 -24.835 -12.765 1.00 20.98 C N
ATOM 7297 CA ASN I 27 22.435 -24.709 -14.004 1.00 19.70 C C
ATOM 7298 CB ASN I 27 22.165 -25.904 -14.928 1.00 20.41 C C
ATOM 7299 CG ASN I 27 22.952 -25.833 -16.231 1.00 23.56 C C
ATOM 7300 OD1 ASN I 27 24.156 -25.579 -16.199 1.00 24.42 C O
ATOM 7301 ND2 ASN I 27 22.227 -25.693 -17.339 1.00 27.70 C N
ATOM 7302 C ASN I 27 22.086 -23.414 -14.727 1.00 18.42 C C
ATOM 7303 O ASN I 27 21.539 -23.447 -15.830 1.00 18.47 C O
ATOM 7304 N ILE I 28 22.230 -22.288 -14.033 1.00 16.54 C N
ATOM 7305 CA ILE I 28 21.853 -21.004 -14.611 1.00 14.59 C C ATOM 7306 CB ILE I 28 21.526 -19.932 -13.546 1.00 14.01 C C
ATOM 7307 CGI ILE I 28 22.461 -20.055 -12.343 1.00 15.60 C C
ATOM 7308 CD 1 ILE I 28 23.710 -19.205 -12.454 1.00 16.26 C C
ATOM 7309 CG2 ILE I 28 20.065 -20.023 -13.122 1.00 12.57 C C
ATOM 7310 C ILE I 28 22.915 -20.484 -15.561 1.00 13.86 C C
ATOM 7311 O ILE I 28 24.111 -20.702 -15.363 1.00 13.70 C O
ATOM 7312 N TH I 29 22.442 -20.013 -16.703 1.00 13.23 C N
ATOM 7313 CA THR I 29 23.301 -19.589 -17.786 1.00 12.65 C C
ATOM 7314 CB THR I 29 23.241 -20.586 -18.948 1.00 12.69 C C
ATOM 7315 OG1 THR I 29 22.805 -21.861 -18.463 1.00 12.62 C O
ATOM 7316 CG2 THR I 29 24.603 -20.727 -19.608 1.00 12.92 C C
ATOM 7317 C THR I 29 22.740 -18.277 -18.281 1.00 12.47 C C
ATOM 7318 O THR I 29 21.531 -18.051 -18.220 1.00 12.53 C O
ATOM 7319 N GLU I 30 23.596 -17.467 -18.884 1.00 11.98 C N
ATOM 7320 CA GLU I 30 23.135 -16.364 -19.702 1.00 11.68 C C
ATOM 7321 CB GLU I 30 23.508 -15.035 -19.049 1.00 11.98 C C
ATOM 7322 CG GLU I 30 22.537 -13.901 -19.321 1.00 13.38 C C
ATOM 7323 CD GLU I 30 22.687 -12.767 -18.325 1.00 16.03 C C
ATOM 7324 OE1 GLU I 30 23.820 -12.269 -18.155 1.00 16.65 C O
ATOM 7325 OE2 GLU I 30 21.684 -12.412 -17.673 1.00 17.06 C O
ATOM 7326 C GLU I 30 23.814 -16.480 -21.047 1.00 11.39 C C
ATOM 7327 O GLU I 30 25.000 -16.799 -21.124 1.00 11.50 C O
ATOM 7328 N GLU I 31 23.036 -16.344 -22.111 1.00 11.11 C N
ATOM 7329 CA GLU I 31 23.626 -16.233 -23.427 1.00 11.06 C C
ATOM 7330 CB GLU I 31 23.376 -17.494 -24.251 1.00 11.48 C C
ATOM 7331 CG GLU I 31 22.395 -17.322 -25.391 1.00 13.90 C C
ATOM 7332 CD GLU I 31 22.329 -18.546 -26.280 1.00 17.27 C C
ATOM 7333 OE1 GLU I 31 22.658 -18.428 -27.478 1.00 17.55 C O
ATOM 7334 OE2 GLU I 31 21.999 -19.638 -25.769 1.00 18.73 C O
ATOM 7335 C GLU I 31 23.177 -14.989 -24.167 1.00 10.47 C C
ATOM 7336 O GLU I 31 22.010 -14.597 -24.118 1.00 10.12 C O
ATOM 7337 N PHE I 32 24.139 -14.352 -24.816 1.00 10.15 C N
ATOM 7338 CA PHE I 32 23.986 -12.994 -25.289 1.00 9.62 C C
ATOM 7339 CB PHE I 32 25.267 -12.204 -25.017 1.00 9.42 C C
ATOM 7340 CG PHE I 32 25.384 -10.939 -25.822 1.00 9.27 C C
ATOM 7341 CD1 PHE I 32 24.529 -9.871 -25.585 1.00 9.37 C C
ATOM 7342 CE1 PHE I 32 24.614 -8.713 -26.339 1.00 9.52 C C
ATOM 7343 CZ PHE I 32 25.594 -8.593 -27.306 1.00 9.82 C C
ATOM 7344 CE2 PHE I 32 26.458 -9.651 -27.548 1.00 10.13 C C
ATOM 7345 CD2 PHE I 32 26.372 -10.802 -26.786 1.00 10.06 C C
ATOM 7346 C PHE I 32 23.715 -13.038 -26.782 1.00 9.64 C C
ATOM 7347 O PHE I 32 24.336 -13.811 -27.512 1.00 9.84 C O
ATOM 7348 N TYR I 33 22.764 -12.229 -27.228 1.00 9.59 C N
ATOM 7349 CA TYR I 33 22.384 -12.221 -28.629 1.00 9.67 C C
ATOM 7350 CB TYR I 33 20.874 -12.414 -28.771 1.00 9.52 C C
ATOM 7351 CG TYR I 33 20.408 -13.802 -28.397 1.00 10.94 C C
ATOM 7352 CD1 TYR I 33 19.978 -14.084 -27.107 1.00 12.23 C C
ATOM 7353 CE1 TYR I 33 19.587 -15.359 -26.750 1.00 12.93 C C
ATOM 7354 CZ TYR I 33 19.675 -16.381 -27.670 1.00 13.47 C C
ATOM 7355 OH TYR I 33 19.297 -17.656 -27.315 1.00 14.54 C O
ATOM 7356 CE2 TYR I 33 20.151 -16.137 -28.941 1.00 13.56 C C
ATOM 7357 CD2 TYR I 33 20.538 -14.858 -29.288 1.00 12.96 C C
ATOM 7358 C TYR I 33 22.832 -10.933 -29.306 1.00 9.94 C C
ATOM 7359 O TYR I 33 22.138 -9.917 -29.257 1.00 10.16 C O
ATOM 7360 N GLN I 34 24.036 -10.964 -29.865 1.00 10.06 C N
ATOM 7361 CA GLN I 34 24.713 -9.751 -30.294 1.00 10.01 C C
ATOM 7362 CB GLN I 34 26.105 -10.085 -30.819 1.00 10.22 C C
ATOM 7363 CG GLN I 34 26.862 -8.884 -31.336 1.00 11.12 C C
ATOM 7364 CD GLN I 34 28.323 -9.187 -31.577 1.00 13.13 C C
ATOM 7365 OE1 GLN I 34 28.674 -9.887 -32.528 1.00 14.24 C O ATOM 7366 NE2 GLN I 34 29.183 -8.693 -30.693 1.00 13.79 C N
ATOM 7367 C GLN I 34 23.914 -9.028 -31.370 1.00 9.94 C C
ATOM 7368 O GLN I 34 24.051 -7.818 -31.550 1.00 10.08 C O
ATOM 7369 N SE I 35 23.079 -9.781 -32.081 1.00 9.87 C N
ATOM 7370 CA SE I 35 22.336 -9.255 -33.225 1.00 9.91 C C
ATOM 7371 CB SE I 35 21.995 -10.382 -34.206 1.00 10.03 C C
ATOM 7372 OG SER I 35 21.241 -11.403 -33.574 1.00 10.81 C O
ATOM 7373 C SER I 35 21.059 -8.555 -32.775 1.00 9.56 C C
ATOM 7374 O SER I 35 20.248 -8.124 -33.595 1.00 9.59 C O
ATOM 7375 N THR I 36 20.823 -8.581 -31.472 1.00 9.21 C N
ATOM 7376 CA THR I 36 19.592 -8.066 -30.903 1.00 9.06 C C
ATOM 7377 CB THR I 36 18.648 -9.214 -30.517 1.00 9.49 C C
ATOM 7378 OG1 THR I 36 18.292 -9.956 -31.691 1.00 10.82 C O
ATOM 7379 CG2 THR I 36 17.392 -8.673 -29.860 1.00 9.45 C C
ATOM 7380 C THR I 36 19.966 -7.274 -29.661 1.00 8.77 C C
ATOM 7381 O THR I 36 19.112 -6.915 -28.848 1.00 8.60 C O
ATOM 7382 N CYS I 37 21.266 -7.035 -29.515 1.00 8.69 C N
ATOM 7383 CA CYS I 37 21.818 -6.428 -28.314 1.00 8.69 C C
ATOM 7384 CB CYS I 37 21.917 -4.911 -28.490 1.00 8.81 C C
ATOM 7385 SG CYS I 37 23.280 -4.138 -27.602 1.00 10.80 C S
ATOM 7386 C CYS I 37 20.954 -6.758 -27.107 1.00 8.27 C C
ATOM 7387 O CYS I 37 20.341 -5.872 -26.513 1.00 8.27 C O
ATOM 7388 N SER I 38 20.825 -8.045 -26.808 1.00 7.92 C N
ATOM 7389 CA SER I 38 19.990 -8.476 -25.699 1.00 7.51 C C
ATOM 7390 CB SER I 38 18.537 -8.626 -26.150 1.00 7.63 C C
ATOM 7391 OG SER I 38 18.429 -9.583 -27.190 1.00 8.54 C O
ATOM 7392 C SER I 38 20.496 -9.784 -25.110 1.00 7.02 C C
ATOM 7393 O SER I 38 21.196 -10.546 -25.776 1.00 6.83 C O
ATOM 7394 N ALA I 39 20.214 -9.995 -23.830 1.00 6.64 C N
ATOM 7395 CA ALA I 39 20.727 -11.159 -23.127 1.00 6.58 C C
ATOM 7396 CB ALA I 39 21.834 -10.761 -22.174 1.00 6.67 C C
ATOM 7397 C ALA I 39 19.615 -11.885 -22.388 1.00 6.93 C C
ATOM 7398 O ALA I 39 18.683 -11.263 -21.878 1.00 7.38 C O
ATOM 7399 N VAL I 40 19.675 -13.211 -22.415 1.00 6.87 C N
ATOM 7400 CA VAL I 40 18.707 -14.034 -21.706 1.00 6.55 C C
ATOM 7401 CB VAL I 40 17.905 -14.928 -22.668 1.00 6.22 C C
ATOM 7402 CGI VAL I 40 17.196 -16.031 -21.899 1.00 6.52 C C
ATOM 7403 CG2 VAL I 40 16.905 -14.098 -23.456 1.00 6.62 C C
ATOM 7404 C VAL I 40 19.394 -14.909 -20.670 1.00 6.73 C C
ATOM 7405 O VAL I 40 20.351 -15.620 -20.977 1.00 6.83 C O
ATOM 7406 N SER I 41 18.916 -14.822 -19.434 1.00 6.86 C N
ATOM 7407 CA SER I 41 19.298 -15.760 -18.388 1.00 6.75 C C
ATOM 7408 CB SER I 41 19.221 -15.082 -17.022 1.00 7.06 C C
ATOM 7409 OG SER I 41 18.745 -13.752 -17.148 1.00 7.50 C O
ATOM 7410 C SER I 41 18.399 -16.988 -18.409 1.00 6.56 C C
ATOM 7411 O SER I 41 17.174 -16.873 -18.403 1.00 6.08 C O
ATOM 7412 N LYS I 42 19.019 -18.163 -18.409 1.00 7.02 C N
ATOM 7413 CA LYS I 42 18.311 -19.409 -18.665 1.00 7.83 C C
ATOM 7414 CB LYS I 42 18.835 -20.066 -19.943 1.00 8.15 C C
ATOM 7415 CG LYS I 42 18.753 -19.192 -21.182 1.00 9.75 C C
ATOM 7416 CD LYS I 42 19.416 -19.872 -22.369 1.00 12.62 C C
ATOM 7417 CE LYS I 42 19.087 -19.162 -23.671 1.00 14.04 C C
ATOM 7418 NZ LYS I 42 19.298 -20.046 -24.851 1.00 14.96 C N
ATOM 7419 C LYS I 42 18.489 -20.367 -17.495 1.00 7.80 C C
ATOM 7420 O LYS I 42 19.512 -20.336 -16.810 1.00 8.15 C O
ATOM 7421 N GLY I 43 17.581 -21.330 -17.389 1.00 7.59 C N
ATOM 7422 CA GLY I 43 17.783 -22.472 -16.508 1.00 7.35 C C
ATOM 7423 C GLY I 43 17.031 -22.326 -15.202 1.00 7.10 C C
ATOM 7424 O GLY I 43 17.428 -22.883 -14.179 1.00 7.13 C O
ATOM 7425 N TYR I 44 15.907 -21.621 -15.253 1.00 7.01 C N ATOM 7426 CA TY I 44 15.095 -21.391 -14.066 1.00 6.89 C c
ATOM 7427 CB TY I 44 14.678 -19.924 -13.982 1.00 6.88 c c
ATOM 7428 CG TYR I 44 15.828 -18.979 -13.738 1.00 6.41 c c
ATOM 7429 CD1 TYR I 44 16.374 -18.238 -14.776 1.00 6.62 c c
ATOM 7430 CE1 TYR I 44 17.430 -17.376 -14.558 1.00 6.48 c c
ATOM 7431 CZ TYR I 44 17.946 -17.240 -13.287 1.00 6.88 c c
ATOM 7432 OH TYR I 44 18.989 -16.371 -13.062 1.00 7.50 c o
ATOM 7433 CE2 TYR I 44 17.438 -17.984 -12.245 1.00 6.68 c c
ATOM 7434 CD2 TYR I 44 16.388 -18.851 -12.475 1.00 5.91 c c
ATOM 7435 C TYR I 44 13.859 -22.275 - 14.065 1.00 6.86 c c
ATOM 7436 O TYR I 44 13.320 -22.602 - 15.122 1.00 7.14 c o
ATOM 7437 N LEU I 45 13.309 -22.498 - 12.875 1.00 6.44 c N
ATOM 7438 CA LEU I 45 12.131 -23.342 -12.733 1.00 6.12 c c
ATOM 7439 CB LEU I 45 12.479 -24.650 -12.019 1.00 6.31 c c
ATOM 7440 CG LEU I 45 13.457 -25.536 -12.798 1.00 6.38 c c
ATOM 7441 CD1 LEU I 45 14.250 -26.452 -11.877 1.00 7.05 c c
ATOM 7442 CD2 LEU I 45 12.736 -26.332 -13.874 1.00 7.05 c c
ATOM 7443 C LEU I 45 10.924 -22.641■ -12.096 1.00 5.84 C c
ATOM 7444 O LEU I 45 10.954 -22.268 -10.921 1.00 5.94 c o
ATOM 7445 N SER I 46 9.806 -22.689 - 12.821 1.00 5.43 c N
ATOM 7446 CA SER I 46 8.639 -21.822 -12.611 1.00 5.26 c c
ATOM 7447 CB SER I 46 7.803 -21.796 -13.891 1.00 5.21 c c
ATOM 7448 OG SER I 46 7.441 -23.112 -14.280 1.00 4.95 c o
ATOM 7449 C SER I 46 7.793 -22.404 - 11.485 1.00 5.51 c c
ATOM 7450 O SER I 46 8.086 -23.500 - 11.013 1.00 6.03 c o
ATOM 7451 N ALA I 47 6.787 -21.679 - ■11.001 1.00 5.24 c N
ATOM 7452 CA ALA I 47 6.265 -22.042 -9.688 1.00 4.83 c c
ATOM 7453 CB ALA I 47 7.391 -22.094 -8.675 1.00 5.01 c c
ATOM 7454 C ALA I 47 5.061 -21.315 -9.106 1.00 4.35 c c
ATOM 7455 O ALA I 47 5.100 -20.099 -8.920 1.00 4.45 c o
ATOM 7456 N LEU I 48 4.246 -22.119 -8.428 1.00 3.67 c N
ATOM 7457 CA LEU I 48 3.120 -21.630 -7.645 1.00 3.15 c c
ATOM 7458 CB LEU I 48 1.802 -21.948 -8.359 1.00 2.78 c c
ATOM 7459 CG LEU I 48 1.785 -21.864 -9.889 1.00 2.18 c c
ATOM 7460 CD1 LEU I 48 0.350 -21.834 -10.383 1.00 2.00 c c
ATOM 7461 CD2 LEU I 48 2.544 -20.643 -10.386 1.00 3.94 c c
ATOM 7462 C LEU I 48 3.128 -22.240■ -6.239 1.00 3.06 c c
ATOM 7463 O LEU I 48 3.433 -23.422 -6.065 1.00 3.27 c o
ATOM 7464 N ARG I 49 2.926 -21.394 -5.233 1.00 2.91 c N
ATOM 7465 CA ARG I 49 2.903 -21.846 -3.846 1.00 2.88 C c
ATOM 7466 CB ARG I 49 3.036 -20.658 -2.887 1.00 2.69 c c
ATOM 7467 CG ARG I 49 3.904 -20.942 -1.663 1.00 2.15 c c
ATOM 7468 CD ARG I 49 3.321 -20.322 -0.404 1.00 2.00 c c
ATOM 7469 NE ARG I 49 2.284 -21.163 0.190 1.00 5.18 c N
ATOM 7470 CZ ARG I 49 1.050 -20.748 0.463 1.00 7.68 c c
ATOM 7471 NH1 ARG I 49 0.699 -19.492 , 0.217 1.00 8.32 c N
ATOM 7472 NH2 ARG I 49 0.181 -21.570 i 1.036 1.00 8.12 c N
ATOM 7473 C ARG I 49 1.625 -22.619 - ■3.544 1.00 3.09 c c
ATOM 7474 O ARG I 49 0.527 -22.170■ -3.873 1.00 3.08 c o
ATOM 7475 N THR I 50 1.774 -23.803 - 2.956 1.00 3.37 c N
ATOM 7476 CA THR I 50 0.625 -24.551 -2.456 1.00 3.55 c c
ATOM 7477 CB THR I 50 0.042 -25.503 -3.512 1.00 3.25 c c
ATOM 7478 OG1 THR I 50 1.091 -26.292 -4.086 1.00 2.66 c o
ATOM 7479 CG2 THR I 50 -0.670 -24.723 -4.605 1.00 3.46 c c
ATOM 7480 C THR I 50 0.919 -25.349 - 1.195 1.00 4.07 c c
ATOM 7481 O THR I 50 0.137 -25.308 - 0.247 1.00 4.35 c o
ATOM 7482 N GLY I 51 1.892 -26.248 - ■1.274 1.00 4.24 c N
ATOM 7483 CA GLY I 51 2.393 -26.864 -0.060 1.00 4.78 c c
ATOM 7484 C GLY I 51 2.414 -25.769 0.981 1.00 4.98 c c
ATOM 7485 O GLY I 51 3.082 -24.754 0.786 1.00 5.00 c o ATOM 7486 N TRP I 52 1.481 -25.829 1.923 1.00 5.34 C N
ATOM 7487 CA TRP I 52 1.440 -24.823 2.974 1.00 5.42 c c
ATOM 7488 CB TRP I 52 0.124 -24.048 2.951 1.00 5.75 c c
ATOM 7489 CG TRP I 52 -0.090 -23.284 1.696 1.00 6.38 c c
ATOM 7490 CD1 TRP I 52 -1.020 -23.544 0.734 1.00 7.27 c c
ATOM 7491 NE1 TRP I 52 -0.899 -22.647 -0.297 1.00 7.46 c N
ATOM 7492 CE2 TRP I 52 0.129 -21.785 -0.018 1.00 7.15 c c
ATOM 7493 CD2 TRP I 52 0.671 -22.164 1.228 1.00 7.02 c c
ATOM 7494 CE3 TRP I 52 1.741 -21.428 1.752 1.00 6.83 c c
ATOM 7495 CZ3 TRP I 52 2.221 -20.347 1.027 1.00 6.73 c c
ATOM 7496 CH2 TRP I 52 1.664 -20.000 -0.214 1.00 7.13 c c
ATOM 7497 CZ2 TRP I 52 0.621 -20.706 -0.751 1.00 6.82 c c
ATOM 7498 C TRP I 52 1.680 -25.408 4.354 1.00 5.34 c c
ATOM 7499 O TRP I 52 1.222 -26.507 4.667 1.00 5.47 c o
ATOM 7500 N TYR I 53 2.237 -24.581 5.227 1.00 5.29 c N
ATOM 7501 CA TYR I 53 2.492 -24.977 6.598 1.00 5.58 c c
ATOM 7502 CB TYR I 53 4.002 -25.087 6.829 1.00 5.51 c c
ATOM 7503 CG TYR I 53 4.401 -25.463 8.239 1.00 6.59 c c
ATOM 7504 CD1 TYR I 53 4.613 -26.791 8.591 1.00 8.25 c c
ATOM 7505 CE1 TYR I 53 5.010 -27.136 9.872 1.00 9.40 c c
ATOM 7506 CZ TYR I 53 5.280 -26.145 10.790 1.00 9.24 c c
ATOM 7507 OH TYR I 53 5.693 -26.480 12.058 1.00 9.61 c o
ATOM 7508 CE2 TYR I 53 5.162 -24.818 10.437 1.00 8.78 c c
ATOM 7509 CD2 TYR I 53 4.758 -24.485 9.157 1.00 7.93 c c
ATOM 7510 C TYR I 53 1.869 -23.950 7.539 1.00 5.74 c c
ATOM 7511 O TYR I 53 2.281 -22.790 7.558 1.00 6.19 c o
ATOM 7512 N THR I 54 0.756 -24.328 8.159 1.00 6.04 c N
ATOM 7513 CA THR I 54 0.075 -23.456 9.109 1.00 6.67 c c
ATOM 7514 CB THR I 54 -1.298 -24.028 9.513 1.00 6.97 c c
ATOM 7515 OG1 THR I 54 -2.247 -23.782 8.467 1.00 7.51 c o
ATOM 7516 CG2 THR I 54 -1.790 -23.384 10.800 1.00 7.98 c c
ATOM 7517 C THR I 54 0.928 -23.266 10.359 1.00 6.97 c c
ATOM 7518 O THR I 54 1.713 -24.141 10.723 1.00 7.32 c o
ATOM 7519 N SER I 55 0.775 -22.120 11.013 1.00 7.24 c N
ATOM 7520 CA SER I 55 1.085 -22.019 12.433 1.00 7.65 c c
ATOM 7521 CB SER I 55 2.589 -21.862 12.654 1.00 7.69 c c
ATOM 7522 OG SER I 55 2.868 -21.507 13.998 1.00 7.51 c o
ATOM 7523 C SER I 55 0.338 -20.878 13.104 1.00 8.03 c c
ATOM 7524 O SER I 55 0.238 -19.778 12.560 1.00 8.43 c o
ATOM 7525 N VAL I 56 -0.094 -21.121 14.335 1.00 8.14 c N
ATOM 7526 CA VAL I 56 -1.029 -20.234 15.006 1.00 8.41 c c
ATOM 7527 CB VAL I 56 -2.209 -21.014 15.598 1.00 8.72 c c
ATOM 7528 CGI VAL I 56 -3.403 -20.094 15.787 1.00 9.29 c c
ATOM 7529 CG2 VAL I 56 -2.569 -22.184 14.695 1.00 9.51 c c
ATOM 7530 C VAL I 56 -0.331 -19.478 16.123 1.00 8.19 c c
ATOM 7531 O VAL I 56 0.075 -20.066 17.122 1.00 8.54 c o
ATOM 7532 N ILE I 57 -0.187 -18.171 15.943 1.00 7.91 c N
ATOM 7533 CA ILE I 57 0.639 -17.368 16.832 1.00 7.64 c c
ATOM 7534 CB ILE I 57 1.675 -16.539 16.051 1.00 7.35 c c
ATOM 7535 CGI ILE I 57 2.612 -17.461 15.262 1.00 7.25 c c
ATOM 7536 CD1 ILE I 57 3.526 -16.730 14.294 1.00 8.42 c c
ATOM 7537 CG2 ILE I 57 2.457 -15.632 16.993 1.00 7.52 c c
ATOM 7538 C ILE I 57 -0.222 -16.445 17.680 1.00 7.69 c c
ATOM 7539 O ILE I 57 -1.150 -15.810 17.178 1.00 7.79 C O
ATOM 7540 N THR I 58 -0.024 -16.523 18.989 1.00 7.85 C N
ATOM 7541 CA THR I 58 -0.929 -15.900 19.938 1.00 8.15 C C
ATOM 7542 CB THR I 58 -1.660 -16.954 20.777 1.00 8.14 C C
ATOM 7543 OG1 THR I 58 -1.584 -18.225 20.120 1.00 8.62 C O
ATOM 7544 CG2 THR I 58 -3.116 -16.566 20.957 1.00 7.94 C C
ATOM 7545 C THR I 58 -0.152 -14.983 20.869 1.00 8.20 C C ATOM 7546 O TH I 58 0.808 -15.408 21.510 1.00 8.18 C O
ATOM 7547 N ILE I 59 -0.539 -13.713 20.903 1.00 8.54 C N
ATOM 7548 CA ILE I 59 0.226 -12.694 21.616 1.00 9.23 C C
ATOM 7549 CB ILE I 59 0.863 -11.690 20.634 1.00 8.92 C C
ATOM 7550 CGI ILE I 59 1.868 -12.391 19.717 1.00 9.27 C C
ATOM 7551 CDHLE I 59 2.587 -11.453 18.770 1.00 10.89 C C
ATOM 7552 CG2 ILE I 59 1.516 -10.544 21.390 1.00 8.74 C C
ATOM 7553 C ILE I 59 -0.691 -11.920 22.553 1.00 10.02 C C
ATOM 7554 O ILE I 59 -1.692 -11.357 22.113 1.00 10.20 C O
ATOM 7555 N GLU I 60 -0.439 -12.007 23.853 1.00 10.95 C N
ATOM 7556 CA GLU I 60 -1.462 -11.602 24.808 1.00 12.13 C C
ATOM 7557 CB GLU I 60 -0.963 -11.829 26.248 1.00 12.44 C C
ATOM 7558 CG GLU I 60 -0.554 -13.288 26.547 1.00 15.04 C C
ATOM 7559 CD GLU I 60 -0.560 -13.630 28.036 1.00 19.34 C C
ATOM 7560 OE1 GLU I 60 0.413 -13.267 28.733 1.00 20.63 C O
ATOM 7561 OE2 GLU I 60 -1.469 -14.368 28.478 1.00 21.19 C O
ATOM 7562 C GLU I 60 -1.856 -10.131 24.547 1.00 12.46 C C
ATOM 7563 O GLU I 60 -0.984 -9.259 24.567 1.00 12.68 C O
ATOM 7564 N LEU I 61 -3.138 -9.818 24.298 1.00 12.80 C N
ATOM 7565 CA LEU I 61 -3.535 -8.473 24.718 1.00 12.71 C C
ATOM 7566 CB LEU I 61 -5.021 -8.120 24.699 1.00 12.55 C C
ATOM 7567 CG LEU I 61 -5.052 -6.753 25.421 1.00 12.39 C C
ATOM 7568 CD1 LEU I 61 -4.358 -5.650 24.625 1.00 13.14 C C
ATOM 7569 CD2 LEU I 61 -6.421 -6.318 25.899 1.00 12.50 C C
ATOM 7570 C LEU I 61 -3.097 -8.585 26.133 1.00 12.94 C C
ATOM 7571 O LEU I 61 -3.578 -9.474 26.843 1.00 12.78 C O
ATOM 7572 N SE I 62 -1.846 -8.190 26.260 1.00 13.61 C N
ATOM 7573 CA SE I 62 -1.183 -8.231 27.527 1.00 14.70 C C
ATOM 7574 CB SER I 62 0.326 -8.252 27.325 1.00 14.52 C C
ATOM 7575 OG SER I 62 0.724 -9.440 26.664 1.00 14.80 C O
ATOM 7576 C SER I 62 -1.605 -6.983 28.261 1.00 15.48 C C
ATOM 7577 O SER I 62 -1.206 -5.880 27.893 1.00 15.50 C O
ATOM 7578 N ASN I 63 -2.602 -7.135 29.121 1.00 16.61 C N
ATOM 7579 CA ASN I 63 -3.232 -5.978 29.716 1.00 17.77 C C
ATOM 7580 CB ASN I 63 -4.616 -6.314 30.263 1.00 17.73 C C
ATOM 7581 CG ASN I 63 -5.566 -5.142 30.175 1.00 18.52 C C
ATOM 7582 OD1 ASN I 63 -5.140 -3.987 30.185 1.00 18.29 C O
ATOM 7583 ND2 ASN I 63 -6.837 -5.433 29.933 1.00 19.40 C N
ATOM 7584 C ASN I 63 -2.369 -5.335 30.787 1.00 18.53 C C
ATOM 7585 O ASN I 63 -1.589 -6.007 31.463 1.00 18.82 C O
ATOM 7586 N ILE I 64 -2.403 -4.010 30.819 1.00 19.60 C N
ATOM 7587 CA ILE I 64 -1.812 -3.252 31.908 1.00 21.04 C C
ATOM 7588 CB ILE I 64 -1.433 -1.836 31.448 1.00 20.60 C C
ATOM 7589 CGI ILE I 64 -0.845 -1.878 30.038 1.00 20.13 C C
ATOM 7590 CDHLE I 64 -0.383 -0.534 29.522 1.00 20.19 C C
ATOM 7591 CG2 ILE I 64 -0.451 -1.211 32.416 1.00 20.74 C C
ATOM 7592 C ILE I 64 -2.778 -3.148 33.082 1.00 22.58 C C
ATOM 7593 O ILE I 64 -3.951 -2.832 32.900 1.00 23.07 C O
ATOM 7594 N LYS I 65 -2.259 -3.322 34.292 1.00 24.21 C N
ATOM 7595 CA LYS I 65 -2.904 -2.779 35.482 1.00 25.86 C C
ATOM 7596 CB LYS I 65 -2.929 -3.822 36.602 1.00 25.90 C C
ATOM 7597 CG LYS I 65 -2.083 -5.056 36.323 1.00 26.69 C C
ATOM 7598 CD LYS I 65 -0.616 -4.698 36.160 1.00 28.26 C C
ATOM 7599 CE LYS I 65 0.273 -5.606 36.992 1.00 28.67 C C
ATOM 7600 NZ LYS I 65 1.600 -4.983 37.247 1.00 28.95 C N
ATOM 7601 C LYS I 65 -2.215 -1.500 35.961 1.00 26.81 C C
ATOM 7602 O LYS I 65 -1.160 -1.557 36.591 1.00 26.72 C O
ATOM 7603 N GLU I 66 -2.903 -0.371 35.798 1.00 27.90 C N
ATOM 7604 CA GLU I 66 -2.291 0.962 35.878 1.00 28.82 C C
ATOM 7605 CB GLU I 66 -3.184 1.983 35.163 1.00 28.88 C C ATOM 7606 CG GLU I 66 -3.354 3.309 35.901 1.00 30.33 C C
ATOM 7607 CD GLU I 66 -4.570 4.084 35.431 1.00 33.17 C C
ATOM 7608 OE1 GLU I 66 -4.590 5.323 35.595 1.00 35.05 C O
ATOM 7609 OE2 GLU I 66 -5.488 3.457 34.860 1.00 33.14 C O
ATOM 7610 C GLU I 66 -2.102 1.393 37.333 1.00 29.12 C C
ATOM 7611 O GLU I 66 -3.002 1.204 38.148 1.00 29.28 C O
ATOM 7612 N ASN I 67 -0.975 2.029 37.653 1.00 29.32 C N
ATOM 7613 CA ASN I 67 -0.630 2.266 39.065 1.00 29.39 C C
ATOM 7614 CB ASN I 67 0.664 1.550 39.473 1.00 29.62 C C
ATOM 7615 CG ASN I 67 0.399 0.206 40.133 1.00 29.84 C C
ATOM 7616 OD1 ASN I 67 -0.154 0.147 41.233 1.00 29.93 C O
ATOM 7617 ND2 ASN I 67 0.655 -0.875 39.400 1.00 29.22 C N
ATOM 7618 C ASN I 67 -0.670 3.712 39.571 1.00 29.15 C C
ATOM 7619 O ASN I 67 0.352 4.281 39.962 1.00 29.06 C O
ATOM 7620 N LYS I 68 -1.872 4.284 39.584 1.00 28.87 C N
ATOM 7621 CA LYS I 68 -2.302 5.212 40.630 1.00 28.78 C C
ATOM 7622 CB LYS I 68 -3.436 4.596 41.454 1.00 28.89 C C
ATOM 7623 CG LYS I 68 -4.461 3.838 40.617 1.00 29.26 C C
ATOM 7624 CD LYS I 68 -5.357 2.964 41.483 1.00 29.68 C C
ATOM 7625 CE LYS I 68 -5.626 3.615 42.835 1.00 29.46 C C
ATOM 7626 NZ LYS I 68 -6.764 2.972 43.555 1.00 29.58 C N
ATOM 7627 C LYS I 68 -1.171 5.722 41.535 1.00 28.60 C C
ATOM 7628 O LYS I 68 -1.082 5.347 42.703 1.00 28.64 C O
ATOM 7629 N CYS I 69 -0.274 6.525 40.961 1.00 28.09 C N
ATOM 7630 CA CYS I 69 0.585 7.455 41.715 1.00 27.63 C C
ATOM 7631 CB CYS I 69 2.068 7.270 41.326 1.00 27.07 C C
ATOM 7632 SG CYS I 69 2.742 8.433 40.058 1.00 28.01 C S
ATOM 7633 C CYS I 69 0.143 8.893 41.433 1.00 27.69 C C
ATOM 7634 O CYS I 69 -0.588 9.134 40.473 1.00 27.41 C O
ATOM 7635 N ASN I 70 0.615 9.855 42.226 1.00 28.06 C N
ATOM 7636 CA ASN I 70 0.603 11.259 41.794 1.00 28.87 C C
ATOM 7637 CB ASN I 70 -0.364 12.119 42.626 1.00 30.52 C C
ATOM 7638 CG ASN I 70 -1.286 11.299 43.518 1.00 39.60 C C
ATOM 7639 OD1 ASN I 70 -2.181 10.602 43.040 1.00 44.97 C O
ATOM 7640 ND2 ASN I 70 -1.073 11.402 44.831 1.00 51.04 C N
ATOM 7641 C ASN I 70 1.978 11.934 41.727 1.00 26.97 C C
ATOM 7642 O ASN I 70 2.563 12.257 42.761 1.00 26.50 C O
ATOM 7643 N GLY I 71 2.371 12.349 40.523 1.00 25.46 C N
ATOM 7644 CA GLY I 71 3.643 13.052 40.316 1.00 23.67 C C
ATOM 7645 C GLY I 71 3.501 14.565 40.288 1.00 22.81 C C
ATOM 7646 O GLY I 71 2.415 15.094 40.516 1.00 22.79 C O
ATOM 7647 N TH I 72 4.585 15.268 39.975 1.00 21.93 C N
ATOM 7648 CA THR I 72 4.526 16.721 39.835 1.00 21.30 C C
ATOM 7649 CB THR I 72 5.923 17.363 39.940 1.00 21.12 C C
ATOM 7650 OG1 THR I 72 6.624 17.194 38.702 1.00 19.87 C O
ATOM 7651 CG2 THR I 72 6.725 16.723 41.063 1.00 20.76 C C
ATOM 7652 C THR I 72 3.864 17.132 38.518 1.00 21.50 C C
ATOM 7653 O THR I 72 4.384 16.852 37.438 1.00 21.85 C O
ATOM 7654 N ASP I 73 2.703 17.774 38.617 1.00 21.43 C N
ATOM 7655 CA ASP I 73 1.767 17.891 37.494 1.00 21.46 C C
ATOM 7656 CB ASP I 73 2.361 18.743 36.368 1.00 21.69 C C
ATOM 7657 CG ASP I 73 1.457 18.812 35.149 1.00 22.46 C C
ATOM 7658 OD1 ASP I 73 0.542 17.969 35.035 1.00 23.01 C O
ATOM 7659 OD2 ASP I 73 1.682 19.690 34.289 1.00 23.09 C O
ATOM 7660 C ASP I 73 1.323 16.536 36.950 1.00 20.96 C C
ATOM 7661 O ASP I 73 2.128 15.792 36.390 1.00 20.61 C O
ATOM 7662 N ALA I 74 0.019 16.285 36.989 1.00 20.42 C N
ATOM 7663 CA ALA I 74 -0.512 14.977 36.622 1.00 20.38 C C
ATOM 7664 CB ALA I 74 -1.027 14.248 37.855 1.00 20.11 C C
ATOM 7665 C ALA I 74 -1.602 15.058 35.556 1.00 20.45 C C ATOM 7666 O ALA I 74 -2.490 14.208 35.509 1.00 20.46 C o
ATOM 7667 N LYS I 75 -1.583 16.114 34.750 1.00 20.67 c N
ATOM 7668 CA LYS I 75 -2.473 16.188 33.596 1.00 20.99 c c
ATOM 7669 CB LYS I 75 -2.421 17.583 32.970 1.00 21.20 c c
ATOM 7670 CG LYS I 75 -2.967 18.684 33.865 1.00 22.02 c c
ATOM 7671 CD LYS I 75 -1.927 19.766 34.106 1.00 23.66 c c
ATOM 7672 CE LYS I 75 -1.971 20.263 35.542 1.00 24.93 c c
ATOM 7673 NZ LYS I 75 -0.622 20.658 36.036 1.00 25.55 c N
ATOM 7674 C LYS I 75 -2.025 15.144 32.587 1.00 20.92 c c
ATOM 7675 O LYS I 75 -2.801 14.680 31.751 1.00 20.92 c o
ATOM 7676 N VAL I 76 -0.731 14.853 32.634 1.00 20.63 c N
ATOM 7677 CA VAL I 76 -0.147 13.700 31.971 1.00 20.36 c c
ATOM 7678 CB VAL I 76 1.386 13.792 32.017 1.00 20.25 c c
ATOM 7679 CGI VAL I 76 2.009 12.475 31.612 1.00 20.82 c : c
ATOM 7680 CG2 VAL I 76 1.873 14.923 31.130 1.00 20.09 c : c
ATOM 7681 C VAL I 76 -0.586 12.393 32.629 1.00 20.29 c c
ATOM 7682 O VAL I 76 -0.452 12.225 33.840 1.00 20.21 c o
ATOM 7683 N LYS I 77 -1.106 11.471 31.826 1.00 20.17 c N
ATOM 7684 CA LYS I 77 -1.642 10.218 32.348 1.00 20.17 c c
ATOM 7685 CB LYS I 77 -3.103 10.393 32.760 1.00 20.62 c c
ATOM 7686 CG LYS I 77 -3.297 10.767 34.215 1.00 23.31 c c
ATOM 7687 CD LYS I 77 -4.508 11.664 34.388 1.00 26.74 c c
ATOM 7688 CE LYS I 77 -4.529 12.291 35.767 1.00 28.32 c c
ATOM 7689 NZ LYS I 77 -5.869 12.836 36.105 1.00 29.66 c N
ATOM 7690 C LYS I 77 -1.523 9.105 31.317 1.00 19.45 c c
ATOM 7691 O LYS I 77 -2.517 8.496 30.921 1.00 19.36 c o
ATOM 7692 N LEU I 78 -0.297 8.863 30.871 1.00 18.70 c N
ATOM 7693 CA LEU I 78 -0.064 8.098 29.659 1.00 17.98 c c
ATOM 7694 CB LEU I 78 1.419 7.775 29.528 1.00 17.72 c c
ATOM 7695 CG LEU I 78 2.275 9.033 29.591 1.00 17.51 c c
ATOM 7696 CD1 LEU I 78 3.746 8.676 29.494 1.00 17.41 c c
ATOM 7697 CD2 LEU I 78 1.859 9.984 28.480 1.00 17.62 c c
ATOM 7698 C LEU I 78 -0.882 6.820 29.656 1.00 17.77 c c
ATOM 7699 O LEU I 78 -1.665 6.576 28.739 1.00 17.89 c o
ATOM 7700 N ILE I 79 -0.749 6.036 30.717 1.00 17.29 C N
ATOM 7701 CA ILE I 79 -1.319 4.703 30.726 1.00 17.00 c c
ATOM 7702 CB ILE I 79 -0.968 3.948 32.005 1.00 16.96 c c
ATOM 7703 CGI ILE I 79 0.550 3.801 32.113 1.00 17.21 c c
ATOM 7704 CD1 ILE I 79 1.020 3.244 33.429 1.00 17.51 c c
ATOM 7705 CG2 ILE I 79 -1.643 2.587 32.005 1.00 17.30 c c
ATOM 7706 C ILE I 79 -2.828 4.750 30.547 1.00 16.83 c c
ATOM 7707 O ILE I 79 -3.365 4.160 29.609 1.00 17.02 c o
ATOM 7708 N LYS I 80 -3.616 5.565 31.220 1.00 16.55 c N
ATOM 7709 CA LYS I 80 -5.043 5.447 30.835 1.00 16.38 c c
ATOM 7710 CB LYS I 80 -5.918 6.332 31.725 1.00 16.73 c c
ATOM 7711 CG LYS I 80 -7.025 7.055 30.971 1.00 17.99 c c
ATOM 7712 CD LYS I 80 -8.237 7.295 31.854 1.00 20.71 c c
ATOM 7713 CE LYS I 80 -9.171 6.094 31.833 1.00 22.92 c c
ATOM 7714 NZ LYS I 80 -8.439 4.818 32.068 1.00 24.75 c N
ATOM 7715 C LYS I 80 -5.386 5.716 29.328 1.00 15.79 c c
ATOM 7716 O LYS I 80 -6.140 4.942 28.677 1.00 15.32 c o
ATOM 7717 N GLN I 81 -4.802 6.770 28.763 1.00 15.48 c N
ATOM 7718 CA GLN I 81 -5.092 7.178 27.383 1.00 15.33 c c
ATOM 7719 CB GLN I 81 -4.378 8.495 27.068 1.00 15.70 c c
ATOM 7720 CG GLN I 81 -4.522 9.557 28.146 1.00 17.88 c c
ATOM 7721 CD GLN I 81 -3.631 10.759 27.903 1.00 20.46 c c
ATOM 7722 OE1 GLN I 81 -3.065 10.916 26.822 1.00 21.59 c o
ATOM 7723 NE2 GLN I 81 -3.498 11.613 28.913 1.00 20.26 C N
ATOM 7724 C GLN I 81 -4.708 6.125 26.341 1.00 14.63 c c
ATOM 7725 O GLN I 81 -5.438 5.881 25.360 1.00 14.60 c o ATOM 7726 N GLU I 82 -3.556 5.500 26.560 1.00 13.81 C N
ATOM 7727 CA GLU I 82 -3.078 4.470 25.657 1.00 13.37 C C
ATOM 7728 CB GLU I 82 -1.705 3.958 26.094 1.00 13.20 C C
ATOM 7729 CG GLU I 82 -0.528 4.666 25.439 1.00 15.04 C C
ATOM 7730 CD GLU I 82 -0.472 4.436 23.942 1.00 17.51 C C
ATOM 7731 OE1 GLU I 82 0.319 3.576 23.502 1.00 18.22 C O
ATOM 7732 OE2 GLU I 82 -1.211 5.121 23.205 1.00 17.87 C O
ATOM 7733 C GLU I 82 -4.079 3.333 25.659 1.00 12.99 C C
ATOM 7734 O GLU I 82 -4.400 2.779 24.610 1.00 12.89 C O
ATOM 7735 N LEU I 83 -4.593 3.001 26.838 1.00 12.89 C N
ATOM 7736 CA LEU I 83 -5.558 1.919 26.944 1.00 13.08 C C
ATOM 7737 CB LEU I 83 -5.923 1.668 28.407 1.00 13.26 C C
ATOM 7738 CG LEU I 83 -4.774 1.250 29.325 1.00 14.18 C C
ATOM 7739 CD1 LEU I 83 -5.293 0.948 30.721 1.00 15.11 C C
ATOM 7740 CD2 LEU I 83 -4.036 0.051 28.748 1.00 14.79 C C
ATOM 7741 C LEU I 83 -6.808 2.252 26.144 1.00 13.18 C C
ATOM 7742 O LEU I 83 -7.310 1.410 25.386 1.00 13.05 C O
ATOM 7743 N ASP I 84 -7.286 3.490 26.251 1.00 13.56 C N
ATOM 7744 CA ASP I 84 -8.478 3.834 25.467 1.00 14.15 C C
ATOM 7745 CB ASP I 84 -8.946 5.258 25.781 1.00 14.80 C C
ATOM 7746 CG ASP I 84 -9.044 5.529 27.268 1.00 18.26 C C
ATOM 7747 OD1 ASP I 84 -10.133 5.330 27.846 1.00 21.11 C O
ATOM 7748 OD2 ASP I 84 -8.032 5.959 27.858 1.00 22.12 C O
ATOM 7749 C ASP I 84 -8.226 3.703 23.954 1.00 13.56 C C
ATOM 7750 O ASP I 84 -9.062 3.149 23.192 1.00 13.70 C O
ATOM 7751 N LYS I 85 -7.062 4.182 23.517 1.00 12.87 C N
ATOM 7752 CA LYS I 85 -6.752 4.121 22.089 1.00 12.31 C C
ATOM 7753 CB LYS I 85 -5.424 4.816 21.793 1.00 12.41 C C
ATOM 7754 CG LYS I 85 -5.118 4.954 20.308 1.00 12.26 C C
ATOM 7755 CD LYS I 85 -3.659 5.305 20.076 1.00 12.72 C C
ATOM 7756 CE LYS I 85 -2.751 4.171 20.519 1.00 14.40 C C
ATOM 7757 NZ LYS I 85 -1.316 4.445 20.230 1.00 16.45 C N
ATOM 7758 C LYS I 85 -6.691 2.671 21.621 1.00 11.85 C C
ATOM 7759 O LYS I 85 -7.187 2.312 20.537 1.00 11.66 C O
ATOM 7760 N TY I 86 -6.085 1.836 22.457 1.00 11.32 C N
ATOM 7761 CA TYR I 86 -5.931 0.432 22.135 1.00 11.07 C C
ATOM 7762 CB TYR I 86 -5.115 -0.290 23.203 1.00 11.12 C C
ATOM 7763 CG TYR I 86 -5.391 -1.773 23.243 1.00 11.30 C C
ATOM 7764 CDI TYR I 86 -4.884 -2.621 22.268 1.00 12.16 C C
ATOM 7765 CE1 TYR I 86 -5.140 -3.977 22.297 1.00 12.39 C C
ATOM 7766 CZ TYR I 86 -5.916 -4.500 23.308 1.00 12.62 C C
ATOM 7767 OH TYR I 86 -6.174 -5.852 23.343 1.00 12.72 C O
ATOM 7768 CE2 TYR I 86 -6.434 -3.680 24.286 1.00 11.38 C C
ATOM 7769 CD2 TYR I 86 -6.173 -2.325 24.248 1.00 11.05 C C
ATOM 7770 C TYR I 86 -7.290 -0.219 22.008 1.00 10.75 C C
ATOM 7771 O TYR I 86 -7.517 -1.004 21.098 1.00 10.45 C O
ATOM 7772 N LYS I 87 -8.204 0.123 22.908 1.00 10.66 C N
ATOM 7773 CA LYS I 87 -9.533 -0.467 22.847 1.00 11.03 C C
ATOM 7774 CB LYS I 87 -10.389 0.010 24.021 1.00 11.36 C C
ATOM 7775 CG LYS I 87 -9.786 -0.270 25.384 1.00 12.79 C C
ATOM 7776 CD LYS I 87 -10.675 0.264 26.495 1.00 14.76 C C
ATOM 7777 CE LYS I 87 -10.068 -0.017 27.859 1.00 15.29 C C
ATOM 7778 NZ LYS I 87 -10.924 0.485 28.970 1.00 16.27 C N
ATOM 7779 C LYS I 87 10.208 -0.098 21.530 1.00 10.83 C C
ATOM 7780 O LYS I 87 10.800 -0.963 20.857 1.00 11.11 C O
ATOM 7781 N ASN I 88 -10.089 1.168 21.126 1.00 10.52 C N
ATOM 7782 CA ASN I 88 -10.721 1.545 19.858 1.00 10.21 C C
ATOM 7783 CB ASN I 88 -10.592 3.050 19.614 1.00 10.61 C C
ATOM 7784 CG ASN I 88 -11.178 3.480 18.281 1.00 11.81 C C
ATOM 7785 OD1 ASN I 88 -12.114 2.864 17.772 1.00 12.97 C O ATOM 7786 ND2 ASN I 88 -10.625 4.543 17.709 1.00 13.82 C N
ATOM 7787 C ASN I 88 10.128 0.767 18.674 1.00 9.42 C C
ATOM 7788 O ASN I 88 ■10.858 0.237 17.796 1.00 8.94 C O
ATOM 7789 N ALA I 89 -8.802 0.652 18.677 1.00 8.77 C N
ATOM 7790 CA ALA I 89 -8.130 -0.041 17.586 1.00 8.21 C C
ATOM 7791 CB ALA I 89 -6.623 0.040 17.751 1.00 7.99 C C
ATOM 7792 C ALA I 89 -8.588 -1.493 17.543 1.00 7.78 C C
ATOM 7793 O ALA I 89 -8.826 -2.057 16.472 1.00 7.88 C O
ATOM 7794 N VAL I 90 -8.718 -2.086 18.724 1.00 7.01 C N
ATOM 7795 CA VAL I 90 -9.124 -3.474 18.849 1.00 6.26 C C
ATOM 7796 CB VAL I 90 -9.079 -3.943 20.313 1.00 5.91 C C
ATOM 7797 CGI VAL I 90 -9.557 -5.381 20.422 1.00 5.92 C C
ATOM 7798 CG2 VAL I 90 -7.671 -3.802 20.871 1.00 5.26 C C
ATOM 7799 C VAL I 90 ■10.524 -3.689 18.299 1.00 6.25 C C
ATOM 7800 O VAL I 90 -10.765 -4.663 17.592 1.00 6.32 C O
ATOM 7801 N TH I 91 ■11.445 -2.776 18.592 1.00 6.24 C N
ATOM 7802 CA THR I 91 -12.799 -2.932 18.065 1.00 6.68 C C
ATOM 7803 CB THR I 91 -13.734 -1.829 18.584 1.00 6.62 C C
ATOM 7804 OG1 THR I 91 -13.711 -1.819 20.017 1.00 7.19 C O
ATOM 7805 CG2 THR I 91 -15.157 -2.071 18.106 1.00 7.27 C C
ATOM 7806 C THR I 91 12.768 -2.885 16.536 1.00 7.02 C C
ATOM 7807 O THR I 91 ■13.430 -3.703 15.833 1.00 7.16 C O
ATOM 7808 N GLU I 92 -11.970 -1.955 16.011 1.00 7.31 C N
ATOM 7809 CA GLU I 92 -11.889 -1.863 14.558 1.00 7.81 C C
ATOM 7810 CB GLU I 92 -11.017 -0.680 14.131 1.00 8.23 C C
ATOM 7811 CG GLU I 92 -11.774 0.630 13.973 1.00 10.91 C C
ATOM 7812 CD GLU I 92 -12.907 0.529 12.969 1.00 14.95 C C
ATOM 7813 OE1 GLU I 92 -12.739 1.010 11.830 1.00 16.14 C O
ATOM 7814 OE2 GLU I 92 -13.968 -0.027 13.320 1.00 16.53 C O
ATOM 7815 C GLU I 92 ■11.349 -3.164 13.959 1.00 7.47 C C
ATOM 7816 O GLU I 92 -11.911 -3.691 12.994 1.00 7.32 C O
ATOM 7817 N LEU I 93 10.303 -3.716 14.568 1.00 7.30 C N
ATOM 7818 CA LEU I 93 -9.703 -4.950 14.062 1.00 7.47 C C
ATOM 7819 CB LEU I 93 -8.429 -5.299 14.830 1.00 7.15 C C
ATOM 7820 CG LEU I 93 -7.212 -4.438 14.490 1.00 7.20 C C
ATOM 7821 CD1 LEU I 93 -5.977 -4.957 15.204 1.00 7.93 C C
ATOM 7822 CD2 LEU I 93 -6.989 -4.392 12.984 1.00 6.91 C C
ATOM 7823 C LEU I 93 10.705 -6.097 14.123 1.00 7.89 C C
ATOM 7824 O LEU I 93 10.764 -6.947 13.235 1.00 7.94 C O
ATOM 7825 N GLN I 94 -11.486 -6.094 15.193 1.00 8.31 C N
ATOM 7826 CA GLN I 94 -12.514 -7.088 15.461 1.00 9.05 C C
ATOM 7827 CB GLN I 94 -13.131 -6.862 16.845 1.00 9.18 C C
ATOM 7828 CG GLN I 94 -12.158 -7.052 17.996 1.00 10.79 C C
ATOM 7829 CD GLN I 94 -12.831 -6.966 19.353 1.00 13.82 C C
ATOM 7830 OE1 GLN I 94 -14.042 -6.762 19.448 1.00 14.98 C O
ATOM 7831 NE2 GLN I 94 -12.047 -7.125 20.412 1.00 15.25 C N
ATOM 7832 C GLN I 94 ■13.615 ■ -7.127 14.405 1.00 9.25 C c
ATOM 7833 O GLN I 94 -14.122 -8.204 14.093 1.00 9.43 c o
ATOM 7834 N LEU I 95 14.007 - ■5.977 13.858 1.00 9.55 c N
ATOM 7835 CA LEU I 95 -15.128 -6.009 12.888 1.00 10.17 c c
ATOM 7836 CB LEU I 95 -15.535 -4.582 12.510 1.00 9.79 c c
ATOM 7837 CG LEU I 95 -16.117 -3.716 13.628 1.00 8.86 c c
ATOM 7838 CD1 LEU I 95 -16.419 -2.315 13.117 1.00 8.31 c c
ATOM 7839 CD2 LEU I 95 -17.367 -4.359 14.211 . 1.00 7.62 c c
ATOM 7840 C LEU I 95 14.958 - 6.865 11.591 1.00 11.22 c c
ATOM 7841 O LEU I 95 15.902 - ■7.505 11.125 1.00 11.55 c o
ATOM 7842 N LEU I 96 13.751 - ■6.843 11.039 1.00 12.40 c N
ATOM 7843 CA LEU I 96 -13.313 -7.374 9.755 1.00 13.66 c c
ATOM 7844 CB LEU I 96 -11.796 -7.246 9.601 1.00 13.38 c c
ATOM 7845 CG LEU I 96 -11.288 -5.847 9.244 1.00 13.32 c c ATOM 7846 CD1 LEU I 96 -9.901 -5.910 8.624 1.00 12.84 C C
ATOM 7847 CD2 LEU I 96 -12.256 -5.161 8.301 1.00 13.38 C C
ATOM 7848 C LEU I 96 -13.765 -8.817 9.534 1.00 14.97 C C
ATOM 7849 O LEU I 96 -13.908 -9.257 8.395 1.00 15.21 C O
ATOM 7850 N MET I 97 -14.125 -9.501 10.615 1.00 16.74 C N
ATOM 7851 CA MET I 97 -14.122 -10.962 10.625 1.00 18.96 C C
ATOM 7852 CB MET I 97 -13.987 -11.498 12.053 1.00 19.12 C C
ATOM 7853 CG MET I 97 -12.742 -11.021 12.784 1.00 21.87 C C
ATOM 7854 SD MET I 97 -11.220 -11.692 12.090 1.00 27.46 C S
ATOM 7855 CE MET I 97 -11.585 -11.630 10.338 1.00 24.25 C C
ATOM 7856 C MET I 97 -15.339 -11.576 9.929 1.00 20.09 C C
ATOM 7857 O MET I 97 -15.246 -12.655 9.343 1.00 20.58 C O
ATOM 7858 N GLN I 98 -16.462 -10.865 9.950 1.00 21.33 C N
ATOM 7859 CA GLN I 98 -17.706 -11.392 9.401 1.00 22.21 C C
ATOM 7860 CB GLN I 98 -18.708 -11.678 10.521 1.00 22.53 C C
ATOM 7861 CG GLN I 98 -18.099 -12.341 11.742 1.00 23.85 C C
ATOM 7862 CD GLN I 98 -17.673 -11.337 12.792 1.00 25.21 C C
ATOM 7863 OE1 GLN I 98 -16.838 -10.469 12.535 1.00 24.47 C O
ATOM 7864 NE2 GLN I 98 -18.199 -11.489 14.002 1.00 24.85 C N
ATOM 7865 C GLN I 98 -18.318 -10.439 8.378 1.00 22.15 C C
ATOM 7866 O GLN I 98 -17.765 -9.376 8.095 1.00 21.77 C O
ATOM 7867 N PHE I 137 -22.709 -16.921 4.271 1.00 33.25 C N
ATOM 7868 CA PHE I 137 -21.644 -16.142 3.651 1.00 36.79 C C
ATOM 7869 CB PHE I 137 -21.061 -16.892 2.453 1.00 20.00 C C
ATOM 7870 CG PHE I 137 -20.354 -18.166 2.825 1.00 20.00 C C
ATOM 7871 CD1 PHE I 137 -19.059 -18.134 3.318 1.00 20.00 C C
ATOM 7872 CE1 PHE I 137 -18.416 -19.301 3.700 1.00 20.00 C C
ATOM 7873 CZ PHE I 137 -19.092 -20.504 3.660 1.00 20.00 C C
ATOM 7874 CE2 PHE I 137 -20.414 -20.534 3.260 1.00 20.00 C C
ATOM 7875 CD2 PHE I 137 -21.046 -19.365 2.871 1.00 20.00 C C
ATOM 7876 C PHE 1 137 -22.138 -14.765 3.226 1.00 48.73 C C
ATOM 7877 O PHE I 137 -21.342 -13.888 2.890 1.00 49.28 C O
ATOM 7878 N LEU I 138 -23.454 -14.580 3.253 1.00 42.04 C N
ATOM 7879 CA LEU I 138 -24.055 -13.275 2.999 1.00 44.26 C C
ATOM 7880 CB LEU I 138 -25.581 -13.366 3.047 1.00 20.00 C C
ATOM 7881 CG LEU I 138 -26.248 -14.219 1.966 1.00 20.00 C C
ATOM 7882 CD1 LEU I 138 -27.748 -14.301 2.197 1.00 20.00 C C
ATOM 7883 CD2 LEU I 138 -25.944 -13.673 0.580 1.00 20.00 C C
ATOM 7884 C LEU 1 138 -23.565 -12.242 4.006 1.00 43.68 C C
ATOM 7885 O LEU I 138 -23.730 -11.038 3.804 1.00 50.27 C O
ATOM 7886 N GLY I 139 -22.983 -12.724 5.100 1.00 38.56 C N
ATOM 7887 CA GLY I 139 -22.415 -11.853 6.126 1.00 47.99 C C
ATOM 7888 C GLY I 139 -21.274 -10.985 5.625 1.00 44.53 C C
ATOM 7889 O GLY I 139 -20.971 -9.947 6.213 1.00 32.21 C O
ATOM 7890 N PHE I 140 -20.649 -11.402 4.528 1.00 46.33 C N
ATOM 7891 CA PHE I 140 -19.494 -10.693 3.986 1.00 42.95 C C
ATOM 7892 CB PHE I 140 -18.549 -11.668 3.281 1.00 20.00 C C
ATOM 7893 CG PHE I 140 -17.916 -12.677 4.202 1.00 20.00 C C
ATOM 7894 CD 1 PHE I 140 -16.781 -12.356 4.929 1.00 20.00 C C
ATOM 7895 CE1 PHE I 140 -16.194 -13.284 5.769 1.00 20.00 C C
ATOM 7896 CZ PHE I 140 -16.731 -14.551 5.879 1.00 20.00 C C
ATOM 7897 CE2 PHE I 140 -17.854 -14.888 5.150 1.00 20.00 C C
ATOM 7898 CD2 PHE I 140 -18.434 -13.958 4.308 1.00 20.00 C C
ATOM 7899 C PHE 1 140 -19.898 -9.568 3.032 1.00 38.13 C C
ATOM 7900 O PHE I 140 -19.052 -8.795 2.581 1.00 57.33 C O
ATOM 7901 N LEU I 141 -21.191 -9.475 2.736 1.00 35.20 C N
ATOM 7902 CA LEU I 141 -21.690 -8.512 1.759 1.00 27.01 C C
ATOM 7903 CB LEU I 141 -21.184 -7.103 2.079 1.00 20.00 C C
ATOM 7904 CG LEU I 141 -21.717 -6.450 3.356 1.00 20.00 C C
ATOM 7905 CD1 LEU I 141 -20.991 -5.144 3.632 1.00 20.00 C C ATOM 7906 CD2 LEU I 141 -23.216 -6.216 3.252 1.00 20.00 C C
ATOM 7907 C LEU 1 141 -21.292 -8.918 0.341 1.00 35.79 C C
ATOM 7908 O LEU I 141 -21.674 -9.989 -0.130 1.00 46.92 C O
ATOM 7909 N LEU I 142 -20.469 -8.099 -0.306 1.00 38.67 C N
ATOM 7910 CA LEU I 142 -19.832 -8.492 -1.559 1.00 33.84 C C
ATOM 7911 CB LEU I 142 -20.017 -7.408 -2.618 1.00 20.00 C C
ATOM 7912 CG LEU I 142 -21.465 -7.163 -3.040 1.00 20.00 C C
ATOM 7913 CD1 LEU I 142 -21.584 -5.883 -3.848 1.00 20.00 C C
ATOM 7914 CD2 LEU I 142 -21.999 -8.350 -3.827 1.00 20.00 C C
ATOM 7915 C LEU 1 142 -18.352 -8.799 -1.363 1.00 36.89 C C
ATOM 7916 O LEU I 142 -17.604 -7.979 -0.831 1.00 45.42 C O
ATOM 7917 N GLY I 143 -17.970 -10.034 -1.673 1.00 26.84 C N
ATOM 7918 CA GLY 1 143 -16.624 -10.516 -1.387 1.00 27.41 C C
ATOM 7919 C GLY I 143 -15.977 -11.154 -2.599 1.00 29.08 C C
ATOM 7920 O GLY I 143 -16.645 -11.813 -3.396 1.00 40.24 C O
ATOM 7921 N VAL I 144 -14.672 -10.957 -2.742 1.00 30.17 C N
ATOM 7922 CA VAL 1 144 -13.928 -11.605 -3.814 1.00 34.15 C C
ATOM 7923 CB VAL I 144 -12.559 -10.921 -4.058 1.00 20.00 C C
ATOM 7924 CGI VAL I 144 -11.826 -11.591 -5.212 1.00 20.00 C C
ATOM 7925 CG2 VAL I 144 -12.750 -9.434 -4.339 1.00 20.00 C C
ATOM 7926 C VAL I 144 -13.732 -13.091 -3.508 1.00 36.67 C C
ATOM 7927 O VAL I 144 -14.071 -13.558 -2.419 1.00 42.49 C O
ATOM 7928 N GLY I 145 -13.320 -13.847 -4.521 1.00 47.09 C N
ATOM 7929 CA GLY 1 145 -12.893 -15.227 -4.321 1.00 44.51 C C
ATOM 7930 C GLY I 145 -11.950 -15.377 -3.141 1.00 44.94 C C
ATOM 7931 O GLY I 145 -12.181 -16.196 -2.253 1.00 40.58 C O
ATOM 7932 N SE I 146 -10.905 -14.560 -3.085 1.00 42.06 C N
ATOM 7933 CA SE I 146 -9.931 -14.673 -2.000 1.00 47.39 C C
ATOM 7934 CB SER I 146 -8.758 -13.718 -2.236 1.00 20.00 C C
ATOM 7935 OG SER I 146 -9.200 -12.373 -2.297 1.00 20.00 C O
ATOM 7936 C SER 1 146 -10.535 -14.425 -0.613 1.00 51.48 C C
ATOM 7937 O SER I 146 -10.211 -15.129 0.351 1.00 47.45 C O
ATOM 7938 N ALA I 147 -11.415 -13.434 -0.514 1.00 39.51 C N
ATOM 7939 C A ALA 1 147 -12.026 -13.082 0.766 1.00 43.38 C C
ATOM 7940 CB ALA I 147 -12.866 -11.821 0.621 1.00 20.00 C C
ATOM 7941 C ALA I 147 -12.865 -14.218 1.348 1.00 47.39 C C
ATOM 7942 O ALA I 147 -12.823 -14.476 2.554 1.00 50.18 C O
ATOM 7943 N ILE I 148 -13.624 -14.894 0.492 1.00 44.67 C N
ATOM 7944 CA ILE I 148 -14.453 -16.007 0.937 1.00 43.56 C C
ATOM 7945 CB ILE I 148 -15.322 -16.558 -0.208 1.00 20.00 C C
ATOM 7946 CGI ILE 1 148 -16.249 -15.466 -0.746 1.00 20.00 C C
ATOM 7947 CD1 ILE 1 148 -17.141 -15.925 -1.878 1.00 20.00 C C
ATOM 7948 CG2 ILE 1 148 -16.127 -17.759 0.265 1.00 20.00 C C
ATOM 7949 C ILE I 148 -13.575 -17.126 1.483 1.00 51.18 C C
ATOM 7950 O ILE I 148 -13.886 -17.736 2.510 1.00 39.17 C O
ATOM 7951 N ALA I 149 -12.468 -17.382 0.794 1.00 42.17 C N
ATOM 7952 CA ALA 1 149 -11.531 -18.412 1.217 1.00 36.76 C C
ATOM 7953 CB ALA I 149 -10.424 -18.578 0.189 1.00 20.00 C C
ATOM 7954 C ALA I 149 -10.949 -18.044 2.574 1.00 45.19 C C
ATOM 7955 O ALA I 149 -10.806 -18.897 3.451 1.00 47.83 C O
ATOM 7956 N SER I 150 -10.632 -16.765 2.748 1.00 43.64 C N
ATOM 7957 CA SER I 150 -10.084 -16.296 4.014 1.00 43.46 C C
ATOM 7958 CB SER I 150 -9.701 -14.818 3.919 1.00 20.00 C C
ATOM 7959 OG SER I 150 -10.828 -14.018 3.605 1.00 20.00 C O
ATOM 7960 C SER I 150 -11.093 -16.507 5.138 1.00 44.80 C C
ATOM 7961 O SER I 150 -10.733 -16.932 6.238 1.00 41.55 C O
ATOM 7962 N GLY I 151 -12.361 -16.222 4.854 1.00 27.01 C N
ATOM 7963 CA GLY 1 151 -13.413 -16.410 5.836 1.00 35.21 C C
ATOM 7964 C GLY I 151 -13.553 -17.871 6.219 1.00 42.40 C C
ATOM 7965 O GLY I 151 -13.742 -18.212 7.394 1.00 45.11 C O ATOM 7966 N VAL I 152 -13.454 -18.742 5.219 1.00 40.20 C N
ATOM 7967 CA VAL 1 152 -13.548 -20.175 5.458 1.00 46.73 C c
ATOM 7968 CB VAL I 152 -13.505 -20.973 4.144 1.00 20.00 c c
ATOM 7969 CGI VAL I 152 -13.606 -22.464 4.426 1.00 20.00 c c
ATOM 7970 CG2 VAL I 152 -14.621 -20.523 3.214 1.00 20.00 c c
ATOM 7971 C VAL I 152 -12.396 -20.615 6.351 1.00 48.62 c c
ATOM 7972 O VAL I 152 -12.579 -21.411 7.273 1.00 49.32 c o
ATOM 7973 N ALA I 153 -11.212 -20.074 6.083 1.00 35.09 c N
ATOM 7974 CA ALA 1 153 -10.030 -20.403 6.867 1.00 42.37 c c
ATOM 7975 CB ALA I 153 -8.798 -19.741 6.274 1.00 20.00 c c
ATOM 7976 C ALA I 153 -10.231 -19.965 8.310 1.00 37.79 c c
ATOM 7977 O ALA I 153 -9.860 -20.676 9.244 1.00 39.25 c o
ATOM 7978 N VAL I 154 -10.825 -18.789 8.486 1.00 38.88 c N
ATOM 7979 CA VAL 1 154 -11.100 -18.270 9.819 1.00 35.53 c c
ATOM 7980 CB VAL I 154 -11.680 -16.845 9.762 1.00 20.00 c c
ATOM 7981 CGI VAL I 154 -11.955 -16.328 11.165 1.00 20.00 c c
ATOM 7982 CG2 VAL I 154 -10.731 -15.916 9.021 1.00 20.00 c c
ATOM 7983 C VAL I 154 -12.071 -19.175 10.572 1.00 41.00 c c
ATOM 7984 O VAL I 154 -11.884 -19.441 11.759 1.00 50.08 c o
ATOM 7985 N SE I 155 -13.105 -19.652 9.882 1.00 37.82 c N
ATOM 7986 CA SER I 155 -14.071 -20.556 10.508 1.00 44.68 c c
ATOM 7987 CB SER I 155 -15.239 -20.834 9.561 1.00 20.00 c c
ATOM 7988 OG SER I 155 -14.790 -21.436 8.360 1.00 20.00 c o
ATOM 7989 C SER 1 155 -13.400 -21.867 10.917 1.00 41.82 c c
ATOM 7990 O SER I 155 -13.667 -22.425 11.982 1.00 49.37 c o
ATOM 7991 N LYS I 156 -12.525 -22.338 10.038 1.00 36.99 c N
ATOM 7992 CA LYS I 156 -11.772 -23.575 10.184 1.00 35.11 c c
ATOM 7993 CB LYS I 156 -11.122 -23.965 8.856 1.00 20.00 c c
ATOM 7994 CG LYS I 156 -12.116 -24.339 7.768 1.00 20.00 c c
ATOM 7995 CD LYS I 156 -11.408 -24.786 6.499 1.00 20.00 c c
ATOM 7996 CE LYS I 156 -12.400 -25.265 5.452 1.00 20.00 c c
ATOM 7997 NZ LYS I 156 -11.733 -25.581 4.158 1.00 20.00 c N
ATOM 7998 C LYS I 156 -10.715 -23.451 11.275 1.00 35.98 c c
ATOM 7999 O LYS 1 156 -10.361 -24.436 11.922 1.00 42.31 c o
ATOM 8000 N VAL I 157 -10.260 -22.224 11.514 1.00 37.88 c N
ATOM 8001 CA VAL 1 157 -9.225 -21.960 12.515 1.00 50.94 c c
ATOM 8002 CB VAL I 157 -8.267 -20.831 12.062 1.00 20.00 c c
ATOM 8003 CGI VAL I 157 -7.261 -20.505 13.162 1.00 20.00 c c
ATOM 8004 CG2 VAL I 157 -7.552 -21.219 10.771 1.00 20.00 c c
ATOM 8005 C VAL I 157 -9.832 -21.596 13.871 1.00 47.82 c c
ATOM 8006 O VAL I 157 -9.116 -21.443 14.863 1.00 56.87 c o
ATOM 8007 N LEU I 158 -11.156 -21.533 13.947 1.00 39.52 c N
ATOM 8008 CA LEU I 158 -11.838 -20.969 15.112 1.00 50.27 c c
ATOM 8009 CB LEU I 158 -13.351 -20.935 14.869 1.00 20.00 c c
ATOM 8010 CG LEU I 158 -13.827 -20.109 13.673 1.00 20.00 c c
ATOM 8011 CD1 LEU I 158 -15.343 -20.163 13.552 1.00 20.00 c c
ATOM 8012 CD2 LEU I 158 -13.346 -18.671 13.788 1.00 20.00 c c
ATOM 8013 C LEU 1 158 -11.550 -21.631 16.465 1.00 54.47 c c
ATOM 8014 O LEU I 158 -11.417 -20.934 17.477 1.00 49.26 c o
ATOM 8015 N HIS I 159 -11.447 -22.954 16.501 1.00 59.45 c N
ATOM 8016 CA HIS I 159 -11.205 -23.636 17.768 1.00 49.11 c c
ATOM 8017 CB HIS I 159 -11.225 -25.153 17.573 1.00 20.00 c c
ATOM 8018 CG HIS I 159 -12.522 -25.676 17.038 1.00 20.00 c c
ATOM 8019 ND1 HIS I 159 -13.559 -26.070 17.855 1.00 20.00 c N
ATOM 8020 CE1 HIS I 159 -14.570 -26.484 17.112 1.00 20.00 c c
ATOM 8021 NE2 HIS 1 159 -14.225 -26.373 15.842 1.00 20.00 c N
ATOM 8022 CD2 HIS I 159 -12.949 -25.871 15.768 1.00 20.00 c c
ATOM 8023 C HIS I 159 -9.874 -23.203 18.385 1.00 44.09 c c
ATOM 8024 O HIS I 159 -9.780 -22.977 19.596 1.00 42.13 c o
ATOM 8025 N LEU I 160 -8.851 -23.072 17.546 1.00 37.55 c N ATOM 8026 CA LEU I 160 -7.536 -22.649 18.011 1.00 43.52 C c
ATOM 8027 CB LEU I 160 -6.520 -22.704 16.869 1.00 20.00 C c
ATOM 8028 CG LEU I 160 -6.299 -24.073 16.224 1.00 20.00 c c
ATOM 8029 CD1 LEU I 160 -5.268 -23.982 15.109 1.00 20.00 c c
ATOM 8030 CD2 LEU I 160 -5.877 -25.097 17.266 1.00 20.00 c c
ATOM 8031 C LEU 1 160 -7.599 -21.240 18.591 1.00 47.22 c c
ATOM 8032 O LEU I 160 -6.984 -20.951 19.619 1.00 43.25 c o
ATOM 8033 N GLU I 161 -8.351 -20.368 17.927 1.00 40.88 c N
ATOM 8034 CA GLU I 161 -8.512 -18.996 18.388 1.00 40.61 c c
ATOM 8035 CB GLU I 161 -9.325 -18.182 17.381 1.00 20.00 c c
ATOM 8036 CG GLU I 161 -8.702 -18.104 15.997 1.00 20.00 c c
ATOM 8037 CD GLU I 161 -9.537 -17.292 15.027 1.00 20.00 c c
ATOM 8038 OE1 GLU I 161 -9.126 -17.158 13.855 1.00 20.00 c o
ATOM 8039 OE2 GLU I 161 -10.604 -16.788 15.436 1.00 20.00 c : o
ATOM 8040 C GLU I 161 -9.195 -18.983 19.749 1.00 39.76 c c
ATOM 8041 O GLU I 161 -8.816 -18.221 20.642 1.00 44.02 c o
ATOM 8042 N GLY I 162 -10.199 -19.840 19.906 1.00 34.18 c N
ATOM 8043 CA GLY I 162 -10.907 -19.934 21.169 1.00 35.01 c c
ATOM 8044 C GLY I 162 -9.967 -20.387 22.269 1.00 34.86 c c
ATOM 8045 O GLY I 162 -9.997 -19.864 23.386 1.00 47.81 c o
ATOM 8046 N GLU I 163 -9.112 -21.352 21.945 1.00 40.78 c N
ATOM 8047 CA GLU 1 163 -8.143 -21.856 22.911 1.00 37.20 c c
ATOM 8048 CB GLU I 163 -7.365 -23.036 22.326 1.00 20.00 c c
ATOM 8049 CG GLU 1 163 -8.235 -24.218 21.931 1.00 20.00 c c
ATOM 8050 CD GLU 1 163 -7.430 -25.368 21.357 1.00 20.00 c c
ATOM 8051 OE1 GLU I 163 -8.037 -26.397 20.995 1.00 20.00 c o
ATOM 8052 OE2 GLU I 163 -6.191 -25.241 21.268 1.00 20.00 c o
ATOM 8053 C GLU I 163 -7.183 -20.745 23.324 1.00 46.12 c c
ATOM 8054 O GLU I 163 -6.837 -20.611 24.501 1.00 58.66 c o
ATOM 8055 N VAL I 164 -6.761 -19.944 22.350 1.00 42.23 c N
ATOM 8056 CA VAL I 164 -5.857 -18.834 22.620 1.00 35.45 c c
ATOM 8057 CB VAL I 164 -5.429 -18.124 21.323 1.00 20.00 c c
ATOM 8058 CGI VAL I 164 -4.487 -16.971 21.635 1.00 20.00 c c
ATOM 8059 CG2 VAL I 164 -4.775 -19.112 20.369 1.00 20.00 c c
ATOM 8060 C VAL I 164 -6.522 -17.823 23.548 1.00 46.32 c c
ATOM 8061 O VAL I 164 -5.892 -17.301 24.472 1.00 45.08 c o
ATOM 8062 N ASN I 165 -7.802 -17.558 23.304 1.00 40.82 c N
ATOM 8063 CA ASN I 165 -8.548 -16.631 24.144 1.00 46.48 c c
ATOM 8064 CB ASN I 165 -9.952 -16.403 23.581 1.00 20.00 c c
ATOM 8065 CG ASN I 165 -9.930 -15.822 22.181 1.00 20.00 c c
ATOM 8066 OD1 ASN I 165 -10.975 -15.504 21.612 1.00 20.00 c o
ATOM 8067 ND2 ASN I 165 -8.736 -15.681 21.617 1.00 20.00 c N
ATOM 8068 C ASN I 165 -8.631 -17.160 25.569 1.00 50.90 c c
ATOM 8069 O ASN I 165 -8.474 -16.412 26.536 1.00 47.11 c o
ATOM 8070 N LYS I 166 -8.857 -18.464 25.688 1.00 48.36 c N
ATOM 8071 CA LYS I 166 -8.945 -19.120 26.986 1.00 38.71 c c
ATOM 8072 CB LYS I 166 -9.329 -20.592 26.818 1.00 20.00 c c
ATOM 8073 CG LYS I 166 -10.649 -20.811 26.097 1.00 20.00 c c
ATOM 8074 CD LYS I 166 -10.952 -22.292 25.936 1.00 20.00 c c
ATOM 8075 CE LYS I 166 -12.264 -22.511 25.200 1.00 20.00 c c
ATOM 8076 NZ LYS I 166 -12.569 -23.958 25.028 1.00 20.00 c N
ATOM 8077 C LYS I 166 -7.623 -19.006 27.738 1.00 45.07 c c
ATOM 8078 O LYS 1 166 -7.600 -18.823 28.955 1.00 56.09 c o
ATOM 8079 N ILE I 167 -6.525 -19.121 26.999 1.00 42.02 C N
ATOM 8080 CA ILE I 167 -5.184 -19.080 27.576 1.00 43.86 c c
ATOM 8081 CB ILE I 167 -4.207 -19.975 26.789 1.00 20.00 c c
ATOM 8082 CGI ILE 1 167 -4.685 -21.429 26.804 1.00 20.00 c c
ATOM 8083 CD1 ILE 1 167 -3.778 -22.377 26.050 1.00 20.00 c c
ATOM 8084 CG2 ILE I 167 -2.803 -19.865 27.362 1.00 20.00 c c
ATOM 8085 C ILE I 167 -4.599 -17.669 27.665 1.00 49.02 c c ATOM 8086 O ILE I 167 -3.448 -17.497 28.066 1.00 37.71 C O
ATOM 8087 N LYS 1 168 -5.382 -16.664 27.282 1.00 33.87 C N
ATOM 8088 CA LYS I 168 -4.890 -15.285 27.251 1.00 35.11 C C
ATOM 8089 CB LYS I 168 -5.939 -14.363 26.622 1.00 20.00 C C
ATOM 8090 CG LYS I 168 -6.275 -14.698 25.178 1.00 20.00 C C
ATOM 8091 CD LYS I 168 -7.292 -13.723 24.607 1.00 20.00 C C
ATOM 8092 CE LYS I 168 -7.612 -14.046 23.157 1.00 20.00 C C
ATOM 8093 NZ LYS I 168 -8.599 -13.092 22.580 1.00 20.00 C N
ATOM 8094 C LYS I 168 -4.431 -14.704 28.600 1.00 39.27 C C
ATOM 8095 O LYS 1 168 -3.414 -14.012 28.655 1.00 32.39 C O
ATOM 8096 N SE I 169 -5.164 -14.973 29.677 1.00 41.30 C N
ATOM 8097 CA SE I 169 -4.797 -14.446 30.987 1.00 43.23 C C
ATOM 8098 CB SER I 169 -5.756 -14.957 32.064 1.00 20.00 C C
ATOM 8099 OG SER I 169 -5.739 -16.371 32.127 1.00 20.00 C O
ATOM 8100 C SER 1 169 -3.359 -14.795 31.353 1.00 41.44 C C
ATOM 8101 O SER I 169 -2.580 -13.924 31.740 1.00 44.82 C O
ATOM 8102 N ALA I 170 -3.013 -16.072 31.235 1.00 39.78 C N
ATOM 8103 CA ALA 1 170 -1.644 -16.517 31.469 1.00 41.01 C C
ATOM 8104 CB ALA I 170 -1.541 -18.025 31.320 1.00 20.00 C C
ATOM 8105 C ALA I 170 -0.674 -15.820 30.523 1.00 46.04 C C
ATOM 8106 O ALA I 170 0.396 -15.373 30.935 1.00 46.67 C O
ATOM 8107 N LEU I 171 -1.061 -15.718 29.258 1.00 34.26 C N
ATOM 8108 CA LEU I 171 -0.245 -15.030 28.269 1.00 37.69 C C
ATOM 8109 CB LEU I 171 -0.942 -15.036 26.912 1.00 20.00 C C
ATOM 8110 CG LEU I 171 -1.226 -16.424 26.346 1.00 20.00 C C
ATOM 8111 CD1 LEU I 171 -1.873 -16.311 24.972 1.00 20.00 C C
ATOM 8112 CD2 LEU I 171 0.060 -17.242 26.293 1.00 20.00 C C
ATOM 8113 C LEU 1 171 0.053 -13.598 28.702 1.00 44.67 C C
ATOM 8114 O LEU I 171 1.173 -13.109 28.538 1.00 34.27 C O
ATOM 8115 N LEU I 172 -0.935 -12.955 29.314 1.00 34.80 C N
ATOM 8116 CA LEU I 172 -0.817 -11.555 29.692 1.00 28.87 C C
ATOM 8117 CB LEU I 172 -2.199 -10.971 29.993 1.00 20.00 C C
ATOM 8118 CG LEU I 172 -3.198 -10.968 28.835 1.00 20.00 C C
ATOM 8119 CD1 LEU I 172 -4.534 -10.393 29.283 1.00 20.00 C C
ATOM 8120 CD2 LEU I 172 -2.643 -10.187 27.668 1.00 20.00 C C
ATOM 8121 C LEU 1 172 0.099 -11.400 30.901 1.00 29.90 C C
ATOM 8122 O LEU I 172 0.896 -10.462 30.972 1.00 41.09 C O
ATOM 8123 N SER I 173 0.016 -12.355 31.824 1.00 35.08 C N
ATOM 8124 CA SER I 173 0.740 -12.276 33.092 1.00 35.53 C C
ATOM 8125 CB SER I 173 0.110 -13.206 34.132 1.00 20.00 C C
ATOM 8126 OG SER I 173 0.148 -14.555 33.701 1.00 20.00 C O
ATOM 8127 C SER 1 173 2.218 -12.610 32.919 1.00 35.07 C C
ATOM 8128 O SER I 173 3.042 -12.300 33.779 1.00 51.28 C O
ATOM 8129 N THR I 174 2.537 -13.275 31.817 1.00 46.35 C N
ATOM 8130 CA THR I 174 3.894 -13.733 31.561 1.00 43.83 C C
ATOM 8131 CB THR I 174 3.889 -14.970 30.641 1.00 20.00 C C
ATOM 8132 OG1 THR I 174 3.327 -14.620 29.371 1.00 20.00 C O
ATOM 8133 CG2 THR I 174 3.056 -16.081 31.260 1.00 20.00 C C
ATOM 8134 C THR I 174 4.722 -12.626 30.910 1.00 52.54 C C
ATOM 8135 O THR I 174 4.393 -12.154 29.821 1.00 64.10 C O
ATOM 8136 N ASN I 175 5.771 -12.188 31.599 1.00 55.57 C N
ATOM 8137 CA ASN I 175 6.735 -11.267 31.008 1.00 40.58 C C
ATOM 8138 CB ASN I 175 7.507 -10.521 32.099 1.00 20.00 C C
ATOM 8139 CG ASN I 175 6.646 -9.518 32.845 1.00 20.00 C C
ATOM 8140 OD1 ASN I 175 5.640 -9.033 32.324 1.00 20.00 C O
ATOM 8141 ND2 ASN I 175 7.043 -9.196 34.072 1.00 20.00 C N
ATOM 8142 C ASN I 175 7.708 -11.986 30.075 1.00 43.65 C C
ATOM 8143 O ASN I 175 8.525 -12.793 30.521 1.00 53.11 C O
ATOM 8144 N LYS 1 176 7.546 -11.768 28.773 1.00 44.89 C N
ATOM 8145 CA LYS I 176 8.402 -12.407 27.776 1.00 46.42 C C ATOM 8146 CB LYS I 176 8.150 -13.917 27.740 1.00 20.00 C C ATOM 8147 CG LYS I 176 8.510 -14.625 29.034 1.00 20.00 C C ATOM 8148 CD LYS I 176 8.270 -16.122 28.943 1.00 20.00 C C ATOM 8149 CE LYS I 176 8.994 -16.863 30.063 1.00 20.00 C C ATOM 8150 NZ LYS I 176 9.447 -18.223 29.648 1.00 20.00 C N ATOM 8151 C LYS I 176 8.192 -11.798 26.392 1.00 45.00 C C ATOM 8152 O LYS 1 176 7.084 -11.379 26.053 1.00 60.64 C O ATOM 8153 N ALA I 177 9.280 -11.645 25.643 1.00 46.01 C N ATOM 8154 CA ALA 1 177 9.189 -11.237 24.242 1.00 43.65 C C ATOM 8155 CB ALA I 177 10.555 -10.847 23.706 1.00 20.00 C C ATOM 8156 C ALA I 177 8.592 -12.349 23.395 1.00 41.42 C C ATOM 8157 O ALA I 177 7.695 -12.116 22.584 1.00 45.37 C O ATOM 8158 N VAL I 178 9.140 -13.549 23.545 1.00 35.70 C N ATOM 8159 CA VAL 1 178 8.580 -14.725 22.902 1.00 43.93 C C ATOM 8160 CB VAL I 178 9.495 -15.243 21.780 1.00 20.00 C C ATOM 8161 CGI VAL I 178 8.898 -16.490 21.143 1.00 20.00 C C ATOM 8162 CG2 VAL I 178 9.714 -14.159 20.734 1.00 20.00 C C ATOM 8163 C VAL I 178 8.363 -15.829 23.922 1.00 34.16 C C ATOM 8164 O VAL I 178 9.115 -15.950 24.889 1.00 44.45 C O ATOM 8165 N VAL I 179 7.271 -16.565 23.760 1.00 44.87 C N ATOM 8166 CA VAL 1 179 6.916 -17.608 24.708 1.00 38.47 C C ATOM 8167 CB VAL I 179 6.234 -17.027 25.960 1.00 20.00 C C ATOM 8168 CGI VAL I 179 5.785 -18.147 26.887 1.00 20.00 C C ATOM 8169 CG2 VAL I 179 7.174 -16.076 26.680 1.00 20.00 C C ATOM 8170 C VAL I 179 6.003 -18.648 24.074 1.00 44.79 C C ATOM 8171 O VAL I 179 5.097 -18.317 23.310 1.00 51.88 C O ATOM 8172 N SE I 180 6.270 -19.911 24.378 1.00 45.23 C N ATOM 8173 CA SE I 180 5.428 -21.002 23.914 1.00 48.99 C C ATOM 8174 CB SE I 180 6.171 -22.334 24.038 1.00 20.00 C C ATOM 8175 OG SER I 180 6.627 -22.542 25.364 1.00 20.00 C O ATOM 8176 C SER I 180 4.118 -21.053 24.698 1.00 48.15 C C ATOM 8177 O SER I 180 4.116 -21.309 25.901 1.00 60.42 C O ATOM 8178 N LEU I 181 3.009 -20.782 24.016 1.00 42.42 C N ATOM 8179 CA LEU I 181 1.684 -20.959 24.605 1.00 43.22 c c ATOM 8180 CB LEU I 181 0.610 -20.369 23.693 1.00 20.00 c c ATOM 8181 CG LEU I 181 0.738 -18.866 23.467 1.00 20.00 c c ATOM 8182 CD1 LEU I 181 -0.514 -18.314 22.808 1.00 20.00 c c ATOM 8183 CD2 LEU I 181 1.008 -18.184 24.795 1.00 20.00 c c ATOM 8184 C LEU 1 181 1.388 -22.428 24.863 1.00 29.14 c c ATOM 8185 O LEU I 181 1.144 -23.194 23.931 1.00 43.42 c o ATOM 8186 N SER I 182 1.361 -22.807 26.136 1.00 41.83 c N ATOM 8187 CA SER I 182 1.272 -24.214 26.503 1.00 53.52 c c ATOM 8188 CB SER I 182 2.491 -24.642 27.324 1.00 20.00 c c ATOM 8189 OG SER I 182 2.601 -23.890 28.521 1.00 20.00 c o ATOM 8190 C SER I 182 -0.025 -24.557 27.236 1.00 44.76 c c ATOM 8191 O SER I 182 -0.492 -23.802 28.090 1.00 37.73 c o ATOM 8192 N ASN I 183 -0.652 -25.649 26.815 1.00 47.84 c N ATOM 8193 CA ASN I 183 -1.684 -26.308 27.603 1.00 59.45 c c ATOM 8194 CB ASN I 183 -3.002 -26.334 26.822 1.00 20.00 c c ATOM 8195 CG ASN I 183 -3.598 -24.951 26.632 1.00 20.00 c c ATOM 8196 OD1 ASN I 183 -3.426 -24.069 27.473 1.00 20.00 c o ATOM 8197 ND2 ASN I 183 -4.381 -24.785 25.572 1.00 20.00 c N ATOM 8198 C ASN I 183 -1.232 -27.732 27.905 1.00 75.41 c c ATOM 8199 O ASN I 183 -0.535 -28.342 27.096 1.00102.31 c o ATOM 8200 N GLY I 184 -1.489 -28.200 29.121 1.00 79.30 c N ATOM 8201 CA GLY I 184 -1.001 -29.510 29.549 1.00 88.92 c c ATOM 8202 C GLY I 184 -0.204 -30.239 28.479 1.00101.85 c c ATOM 8203 O GLY I 184 -0.764 -30.990 27.680 1.00113.48 c o ATOM 8204 N VAL I 185 1.103 -29.994 28.448 1.00 86.84 c N ATOM 8205 CA VAL 1 185 2.047 -30.825 27.696 1.00 81.80 c c ATOM 8206 CB VAL I 185 1.899 -32.323 28.027 1.00 20.00 C c
ATOM 8207 CGI VAL I 185 2.803 -33.155 27.126 1.00 20.00 c c
ATOM 8208 CG2 VAL I 185 2.219 -32.578 29.491 1.00 20.00 c c
ATOM 8209 C VAL I 185 1.997 -30.638 26.179 1.00 81.69 c c
ATOM 8210 O VAL I 185 2.634 -31.388 25.439 1.00 99.84 c o
ATOM 8211 N SE I 186 1.282 -29.618 25.718 1.00 70.63 c N
ATOM 8212 CA SE I 186 1.132 -29.398 24.284 1.00 72.29 c c
ATOM 8213 CB SE I 186 -0.201 -29.962 23.792 1.00 20.00 c c
ATOM 8214 OG SER I 186 -1.291 -29.357 24.467 1.00 20.00 c o
ATOM 8215 C SER I 186 1.247 -27.923 23.915 1.00 62.99 c c
ATOM 8216 O SER I 186 0.649 -27.064 24.565 1.00 58.35 c o
ATOM 8217 N VAL I 187 2.013 -27.638 22.865 1.00 66.49 c N
ATOM 8218 CA VAL I 187 2.203 -26.266 22.398 1.00 57.36 c c
ATOM 8219 CB VAL I 187 3.581 -26.078 21.735 1.00 20.00 c c
ATOM 8220 CGI VAL I 187 3.748 -24.643 21.256 1.00 20.00 c c
ATOM 8221 CG2 VAL I 187 4.691 -26.452 22.699 1.00 20.00 c c
ATOM 8222 C VAL I 187 1.116 -25.863 21.405 1.00 53.67 c c
ATOM 8223 O VAL I 187 0.949 -26.501 20.365 1.00 50.10 c o
ATOM 8224 N LEU I 188 0.381 -24.803 21.731 1.00 43.20 c N
ATOM 8225 CA LEU I 188 -0.676 -24.302 20.858 1.00 41.76 c c
ATOM 8226 CB LEU I 188 -1.749 -23.580 21.674 1.00 20.00 c c
ATOM 8227 CG LEU I 188 -2.557 -24.455 22.632 1.00 20.00 c c
ATOM 8228 CD1 LEU I 188 -3.533 -23.609 23.429 1.00 20.00 c c
ATOM 8229 CD2 LEU I 188 -3.287 -25.542 21.865 1.00 20.00 c c
ATOM 8230 C LEU 1 188 -0.102 -23.361 19.813 1.00 44.75 c c
ATOM 8231 O LEU I 188 -0.674 -23.184 18.738 1.00 45.28 c o
ATOM 8232 N THR I 189 1.054 -22.786 20.124 1.00 39.28 c N
ATOM 8233 CA THR I 189 1.675 -21.805 19.250 1.00 36.51 c c
ATOM 8234 CB THR I 189 0.614 -20.957 18.526 1.00 20.00 c c
ATOM 8235 OG1 THR I 189 -0.113 -20.177 19.481 1.00 20.00 c o
ATOM 8236 CG2 THR I 189 -0.360 -21.858 17.785 1.00 20.00 c c
ATOM 8237 C THR I 189 2.615 -20.901 20.039 1.00 45.83 c c
ATOM 8238 O THR I 189 3.150 -21.304 21.072 1.00 42.57 c o
ATOM 8239 N SER I 190 2.853 -19.698 19.530 1.00 40.44 c N
ATOM 8240 CA SER I 190 3.792 -18.785 20.166 1.00 41.82 c c
ATOM 8241 CB SER I 190 5.022 -18.584 19.283 1.00 20.00 c c
ATOM 8242 OG SER I 190 4.664 -18.015 18.038 1.00 20.00 c o
ATOM 8243 C SER 1 190 3.146 -17.444 20.491 1.00 33.81 c c
ATOM 8244 O SER I 190 2.391 -16.897 19.687 1.00 49.61 c o
ATOM 8245 N LYS I 191 3.454 -16.920 21.674 1.00 37.37 c N
ATOM 8246 CA LYS I 191 2.986 -15.598 22.086 1.00 41.23 c c
ATOM 8247 CB LYS I 191 2.358 -15.664 23.478 1.00 20.00 c c
ATOM 8248 CG LYS I 191 1.069 -16.459 23.525 1.00 20.00 c c
ATOM 8249 CD LYS I 191 0.505 -16.514 24.931 1.00 20.00 c c
ATOM 8250 CE LYS I 191 -0.626 -17.531 25.037 1.00 20.00 c c
ATOM 8251 NZ LYS I 191 -0.791 -18.032 26.435 1.00 20.00 c N
ATOM 8252 C LYS I 191 4.112 -14.568 22.069 1.00 35.03 c c
ATOM 8253 O LYS 1 191 5.120 -14.728 22.757 1.00 40.06 c o
ATOM 8254 N VAL I 192 3.920 -13.495 21.308 1.00 33.70 c N
ATOM 8255 CA VAL 1 192 4.967 -12.498 21.120 1.00 27.61 c c
ATOM 8256 CB VAL I 192 5.392 -12.392 19.646 1.00 20.00 c c
ATOM 8257 CGI VAL I 192 6.395 -11.267 19.465 1.00 20.00 c c
ATOM 8258 CG2 VAL I 192 5.972 -13.709 19.165 1.00 20.00 c c
ATOM 8259 C VAL I 192 4.550 -11.121 21.624 1.00 31.74 c c
ATOM 8260 O VAL I 192 3.376 -10.755 21.573 1.00 25.58 c o
ATOM 8261 N LEU I 193 5.526 -10.364 22.114 1.00 28.88 c N
ATOM 8262 CA LEU I 193 5.316 -8.973 22.488 1.00 34.36 c c
ATOM 8263 CB LEU I 193 5.118 -8.855 23.998 1.00 20.00 c c
ATOM 8264 CG LEU I 193 3.893 -9.566 24.567 1.00 20.00 c c
ATOM 8265 CD1 LEU I 193 3.915 -9.514 26.084 1.00 20.00 c c ATOM 8266 CD2 LEU I 193 2.623 -8.947 24.019 1.00 20.00 C C
ATOM 8267 C LEU 1 193 6.507 -8.126 22.059 1.00 33.03 C C
ATOM 8268 O LEU I 193 7.592 -8.238 22.627 1.00 44.93 C O
ATOM 8269 N ASP 1 194 6.304 -7.294 21.042 1.00 35.09 C N
ATOM 8270 CA ASP I 194 7.409 -6.702 20.288 1.00 41.39 C C
ATOM 8271 CB ASP I 194 6.892 -6.027 19.014 1.00 20.00 C C
ATOM 8272 CG ASP I 194 6.375 -7.023 17.994 1.00 20.00 C C
ATOM 8273 OD1 ASP I 194 6.659 -8.229 18.141 1.00 20.00 C O
ATOM 8274 OD2 ASP I 194 5.654 -6.606 17.064 1.00 20.00 C O
ATOM 8275 C ASP 1 194 8.255 -5.712 21.094 1.00 38.04 C C
ATOM 8276 O ASP 1 194 9.349 -5.339 20.670 1.00 48.03 C O
ATOM 8277 N LEU I 195 7.723 -5.232 22.215 1.00 43.64 C N
ATOM 8278 CA LEU I 195 8.360 -4.139 22.947 1.00 35.97 C C
ATOM 8279 CB LEU I 195 7.417 -2.935 23.045 1.00 20.00 C C
ATOM 8280 CG LEU I 195 7.024 -2.281 21.714 1.00 20.00 C C
ATOM 8281 CD1 LEU I 195 5.965 -1.195 21.915 1.00 20.00 C C
ATOM 8282 CD2 LEU I 195 8.249 -1.730 20.980 1.00 20.00 C C
ATOM 8283 C LEU 1 195 8.858 -4.546 24.335 1.00 43.63 C C
ATOM 8284 O LEU I 195 9.609 -3.811 24.972 1.00 34.71 C O
ATOM 8285 N ASN I 196 8.535 -5.769 24.742 1.00 44.30 C N
ATOM 8286 CA ASN I 196 8.824 -6.238 26.095 1.00 42.38 C C
ATOM 8287 CB ASN I 196 8.399 -7.701 26.254 1.00 20.00 C C
ATOM 8288 CG ASN I 196 6.892 -7.874 26.221 1.00 20.00 C C
ATOM 8289 OD1 ASN I 196 6.146 -6.952 26.545 1.00 20.00 C O
ATOM 8290 ND2 ASN I 196 6.438 -9.055 25.817 1.00 20.00 C N
ATOM 8291 C ASN I 196 10.282 -6.058 26.511 1.00 43.66 C C
ATOM 8292 O ASN I 196 10.568 -5.610 27.622 1.00 33.62 C O
ATOM 8293 N ASN I 197 11.199 -6.448 25.633 1.00 34.31 C N
ATOM 8294 CA ASN I 197 12.621 -6.414 25.950 1.00 38.83 C C
ATOM 8295 CB ASN I 197 13.437 -7.021 24.812 1.00 20.00 C C
ATOM 8296 CG ASN I 197 13.306 -8.527 24.747 1.00 20.00 C C
ATOM 8297 OD1 ASN I 197 13.064 -9.180 25.764 1.00 20.00 C O
ATOM 8298 ND2 ASN I 197 13.315 -9.069 23.533 1.00 20.00 C N
ATOM 8299 C ASN I 197 13.106 -5.005 26.239 1.00 39.90 C C
ATOM 8300 O ASN I 197 13.745 -4.752 27.261 1.00 39.04 C O
ATOM 8301 N TY I 198 12.824 -4.095 25.314 1.00 35.09 C N
ATOM 8302 CA TY I 198 13.109 -2.682 25.518 1.00 41.03 C C
ATOM 8303 CB TY I 198 12.610 -1.859 24.332 1.00 20.00 C C
ATOM 8304 CG TYR I 198 13.298 -2.189 23.031 1.00 20.00 C C
ATOM 8305 CD 1 TYR I 198 14.497 -1.579 22.687 1.00 20.00 C C
ATOM 8306 CE1 TYR I 198 15.110 -1.847 21.488 1.00 20.00 C C
ATOM 8307 CZ TYR I 198 14.536 -2.752 20.620 1.00 20.00 C C
ATOM 8308 OH TYR 1 198 15.138 -3.016 19.411 1.00 20.00 C O
ATOM 8309 CE2 TYR I 198 13.349 -3.378 20.941 1.00 20.00 C C
ATOM 8310 CD2 TYR I 198 12.749 -3.109 22.148 1.00 20.00 C C
ATOM 8311 C TYR I 198 12.490 -2.163 26.811 1.00 43.65 C C
ATOM 8312 O TYR I 198 13.128 -1.410 27.549 1.00 52.37 C O
ATOM 8313 N ILE I 199 11.279 -2.622 27.115 1.00 35.86 C N
ATOM 8314 CA ILE I 199 10.573 -2.185 28.316 1.00 45.39 C C
ATOM 8315 CB ILE I 199 9.108 -2.624 28.306 1.00 20.00 C C
ATOM 8316 CGI ILE 1 199 8.330 -1.808 27.272 1.00 20.00 C C
ATOM 8317 CD1 ILE I 199 7.307 -2.607 26.505 1.00 20.00 C C
ATOM 8318 CG2 ILE I 199 8.502 -2.461 29.691 1.00 20.00 C C
ATOM 8319 C ILE I 199 11.232 -2.684 29.595 1.00 37.89 C C
ATOM 8320 O ILE I 199 11.344 -1.943 30.572 1.00 45.28 C O
ATOM 8321 N ASP 1 200 11.628 -3.953 29.597 1.00 37.36 C N
ATOM 8322 CA ASP 1 200 12.325 -4.543 30.737 1.00 46.66 C C
ATOM 8323 CB ASP 1 200 12.549 -6.040 30.507 1.00 20.00 C C
ATOM 8324 CG ASP 1 200 11.269 -6.841 30.616 1.00 20.00 C C
ATOM 8325 OD1 ASP I 200 10.283 -6.314 31.172 1.00 20.00 C O ATOM 8326 OD2 ASP I 200 11.248 -7.996 30.143 1.00 20.00 C o
ATOM 8327 C ASP I 200 13.655 -3.842 31.033 1.00 51.05 C c
ATOM 8328 O ASP I 200 14.077 -3.753 32.188 1.00 57.39 c o
ATOM 8329 N LYS I 201 14.284 -3.306 29.989 1.00 57.68 c N
ATOM 8330 CA LYS I 201 15.560 -2.605 30.126 1.00 44.02 c c
ATOM 8331 CB LYS I 201 16.228 -2.417 28.760 1.00 20.00 c c
ATOM 8332 CG LYS I 201 16.590 -3.716 28.055 1.00 20.00 c c
ATOM 8333 CD LYS I 201 17.363 -3.463 26.764 1.00 20.00 c c
ATOM 8334 CE LYS I 201 17.644 -4.764 26.018 1.00 20.00 c c
ATOM 8335 NZ LYS I 201 18.195 -4.531 24.654 1.00 20.00 c N
ATOM 8336 C LYS I 201 15.409 -1.254 30.827 1.00 43.56 c c
ATOM 8337 O LYS I 201 16.366 -0.743 31.407 1.00 51.34 c o
ATOM 8338 N GLN I 202 14.202 -0.694 30.795 1.00 46.06 c N
ATOM 8339 CA GLN I 202 13.987 0.689 31.223 1.00 44.95 c c
ATOM 8340 CB GLN I 202 13.366 1.518 30.101 1.00 20.00 c c
ATOM 8341 CG GLN I 202 14.344 1.932 29.024 1.00 20.00 c c
ATOM 8342 CD GLN I 202 13.660 2.551 27.823 1.00 20.00 c c
ATOM 8343 OE1 GLN I 202 12.435 2.519 27.702 1.00 20.00 c o
ATOM 8344 NE2 GLN I 202 14.452 3.135 26.932 1.00 20.00 c N
ATOM 8345 C GLN I 202 13.142 0.816 32.489 1.00 42.35 c c
ATOM 8346 O GLN I 202 13.166 1.853 33.151 1.00 47.00 c o
ATOM 8347 N LEU I 203 12.318 -0.189 32.766 1.00 49.55 c N
ATOM 8348 CA LEU I 203 11.397 -0.111 33.895 1.00 50.77 c c
ATOM 8349 CB LEU I 203 10.332 -1.205 33.796 1.00 20.00 c c
ATOM 8350 CG LEU I 203 9.392 -1.066 32.594 1.00 20.00 c c
ATOM 8351 CD1 LEU I 203 8.616 -2.347 32.316 1.00 20.00 c c
ATOM 8352 CD2 LEU I 203 8.447 0.111 32.787 1.00 20.00 c c
ATOM 8353 C LEU I 203 12.134 -0.184 35.231 1.00 52.51 c c
ATOM 8354 O LEU I 203 13.096 -0.937 35.379 1.00 46.02 c o
ATOM 8355 N LEU I 204 11.747 0.686 36.159 1.00 51.45 c N
ATOM 8356 CA LEU I 204 12.308 0.682 37.507 1.00 58.44 c c
ATOM 8357 CB LEU I 204 12.055 2.021 38.187 1.00 20.00 c c
ATOM 8358 CG LEU I 204 12.780 3.206 37.565 1.00 20.00 c c
ATOM 8359 CD1 LEU I 204 12.380 4.480 38.291 1.00 20.00 c c
ATOM 8360 CD2 LEU I 204 14.286 2.982 37.637 1.00 20.00 c c
ATOM 8361 C LEU I 204 11.700 -0.425 38.354 1.00 54.99 c c
ATOM 8362 O LEU I 204 10.489 -0.633 38.319 1.00 55.13 c o
ATOM 8363 N PRO I 205 12.498 -0.979 39.277 1.00 58.64 c N
ATOM 8364 CA PRO I 205 12.014 -2.145 39.995 1.00 52.19 c c
ATOM 8365 CB PRO I 205 13.198 -2.496 40.896 1.00 20.00 c c
ATOM 8366 CG PRO I 205 13.924 -1.175 41.116 1.00 20.00 c c
ATOM 8367 CD PRO I 205 13.404 -0.175 40.112 1.00 20.00 c c
ATOM 8368 C PRO I 205 10.799 -1.765 40.840 1.00 54.30 c c
ATOM 8369 O PRO I 205 10.014 -2.630 41.235 1.00 70.22 c o
ATOM 8370 N ILE I 206 10.656 -0.465 41.096 1.00 62.70 c N
ATOM 8371 CA ILE I 206 9.491 0.087 41.787 1.00 68.19 c c
ATOM 8372 CB ILE I 206 9.725 0.181 43.311 1.00 20.00 c c
ATOM 8373 CGI ILE I 206 9.753 -1.214 43.941 1.00 20.00 c c
ATOM 8374 CD1 ILE I 206 10.200 -1.220 45.389 1.00 20.00 c c
ATOM 8375 CG2 ILE I 206 8.656 1.047 43.966 1.00 20.00 c c
ATOM 8376 C ILE I 206 9.175 1.484 41.253 1.00 62.35 c c
ATOM 8377 O ILE I 206 10.081 2.268 40.973 1.00 67.16 C 0
ATOM 8378 N VAL I 207 7.894 1.749 41.015 1.00 52.22 c N
ATOM 8379 CA VAL I 207 7.461 3.050 40.521 1.00 51.31 c c
ATOM 8380 CB VAL I 207 6.469 2.918 39.345 1.00 20.00 c c
ATOM 8381 CGI VAL I 207 5.891 4.279 38.984 1.00 20.00 c c
ATOM 8382 CG2 VAL I 207 7.149 2.291 38.139 1.00 20.00 c c
ATOM 8383 C VAL I 207 6.800 3.846 41.634 1.00 62.09 c c
ATOM 8384 O VAL I 207 5.644 3.607 41.980 1.00 58.88 c o
ATOM 8385 N ASN I 208 7.557 4.759 42.229 1.00 71.72 c N ATOM 8386 CA ASNI208 7.023 5.62543.267 1.0070.92 C c
ATOM 8387 CB ASNI208 8.004 5.721 44.433 1.0020.00 c c
ATOM 8388 CG ASNI208 8.100 4.42845.222 1.0020.00 c c
ATOM 8389 OD1 ASNI208 7.170 3.62045.228 1.0020.00 c o
ATOM 8390 ND2 ASN I 208 9.234 4.221 45.884 1.0020.00 c N
ATOM 8391 C ASN I 208 6.699 7.01542.735 1.0063.05 c c
ATOM 8392 O ASN I 208 6.780 7.26441.532 1.0061.34 c o
ATOM 8393 N LYSI209 6.391 7.93343.645 1.0068.91 c N
ATOM 8394 CA LYS I 209 5.953 9.27343.274 1.0059.11 c c
ATOM 8395 CB LYS I 209 5.349 9.99244.482 1.0020.00 c c
ATOM 8396 CG LYS I 209 4.044 9.391 44.979 1.0020.00 c c
ATOM 8397 CD LYS I 209 3.507 10.15846.179 1.0020.00 c c
ATOM 8398 CE LYS I 209 2.159 9.61246.629 1.0020.00 c c
ATOM 8399 NZ LYS I 209 1.583 10.38547.765 1.0020.00 c N
ATOM 8400 C LYS I 209 7.100 10.10042.702 1.0050.69 c c
ATOM 8401 O LYS I 209 6.883 11.17842.152 1.0051.01 c o
ATOM 8402 N GLNI210 8.326 9.63842.920 1.0044.68 c N
ATOM 8403 CA GLNI210 9.495 10.29342.349 1.0049.52 c c
ATOM 8404 CB GLNI210 10.724 10.05243.223 1.0020.00 c c
ATOM 8405 CG GLNI210 10.667 10.73944.573 1.0020.00 c c
ATOM 8406 CD GLNI210 11.865 10.40945.435 1.0020.00 c c
ATOM 8407 OE1 GLNI210 12.517 9.38545.239 1.0020.00 c o
ATOM 8408 NE2GLNI210 12.173 11.28646.383 1.0020.00 C N
ATOM 8409 C GLNI210 9.755 9.78640.938 1.0062.08 c c
ATOM 8410 O GLNI210 9.786 10.560 39.983 1.0080.43 c o
ATOM 8411 N SE I211 9.902 8.47240.813 1.0058.92 c N
ATOM 8412 CA SE I211 10.076 7.84039.514 1.0047.88 c c
ATOM 8413 CB SE I211 9.987 6.319 39.647 1.0020.00 c c
ATOM 8414 OG SE I211 8.735 5.93040.184 1.0020.00 c o
ATOM 8415 C SERI211 9.050 8.34438.503 1.0057.32 c c
ATOM 8416 O SERI211 9.372 8.538 37.331 1.0050.74 c o
ATOM 8417 N CYSI212 7.845 8.647 38.979 1.0044.34 c N
ATOM 8418 CA CYSI212 6.690 8.758 38.095 1.0057.52 c c
ATOM 8419 CB CYSI212 5.453 9.307 38.834 1.0020.00 c c
ATOM 8420 SG CYS I 212 4.771 8.19840.141 1.0020.00 c s
ATOM 8421 C CYS I 212 7.005 9.537 36.808 1.0060.91 c c
ATOM 8422 O CYS I 212 6.991 8.95235.727 1.0052.17 c o
ATOM 8423 N SERI213 7.305 10.827 36.916 1.0021.55 c N
ATOM 8424 CA SERI213 7.501 11.62435.711 1.0021.67 c c
ATOM 8425 CB SERI213 7.747 13.090 36.075 1.0021.81 c c
ATOM 8426 OG SERI213 6.648 13.63036.788 1.0023.00 c o
ATOM 8427 C SERI213 8.650 11.098 34.858 1.0021.45 c c
ATOM 8428 O SERI213 8.509 10.969 33.640 1.0021.98 c o
ATOM 8429 N ILEI214 9.775 10.77235.484 1.0020.90 c N
ATOM 8430 CA ILEI214 10.875 10.168 34.746 1.0020.45 c c
ATOM 8431 CB ILEI214 12.127 10.002 35.624 1.0020.53 c c
ATOM 8432 CGI ILEI214 12.599 11.363 36.141 1.0020.46 c c
ATOM 8433 CD1 ILEI214 13.831 11.289 37.016 1.0021.75 c c
ATOM 8434 CG2ILEI214 13.235 9.309 34.846 1.0020.34 c c
ATOM 8435 C ILEI214 10.423 8.80234.247 1.0020.15 c c
ATOM 8436 O ILEI214 10.647 8.427 33.090 1.0019.91 c o
ATOM 8437 N SERI215 9.751 8.075 35.136 1.0019.84 c N
ATOM 8438 CA SERI215 9.240 6.749 34.827 1.0019.58 c c
ATOM 8439 CB SERI215 8.632 6.10436.073 1.0019.76 c c
ATOM 8440 OG SERI215 8.132 4.81035.785 1.0019.97 c o
ATOM 8441 C SERI215 8.201 6.841 33.724 1.0019.34 c c
ATOM 8442 O SERI215 8.172 6.013 32.818 1.0019.54 c o
ATOM 8443 N ASN I 216 7.351 7.858 33.804 1.0018.80 c N
ATOM 8444 CA ASN I 216 6.324 8.059 32.796 1.0018.36 c c
ATOM 8445 CB ASN I 216 5.406 9.218 33.187 1.0018.41 c c ATOM 8446 CG ASNI216 4.701 8.983 34.508 1.0019.55 C c
ATOM 8447 OD1 ASNI216 3.922 9.819 34.967 1.0020.52 c o
ATOM 8448 ND2 ASNI216 4.971 7.84035.128 1.0020.43 c N
ATOM 8449 C ASNI216 6.958 8.32431.440 1.0017.78 c c
ATOM 8450 O ASNI216 6.509 7.80030.421 1.0017.91 c o
ATOM 8451 N ILEI217 8.016 9.13031.433 1.0017.02 C N
ATOM 8452 CA ILEI217 8.714 9.439 30.194 1.0016.60 c c
ATOM 8453 CB ILEI217 9.833 10.47230.417 1.0016.46 c c
ATOM 8454 CGI ILEI217 9.252 11.77630.969 1.0016.26 c c
ATOM 8455 CD1 ILEI217 10.289 12.849 31.217 1.0016.44 c c
ATOM 8456 CG2ILEI217 10.589 10.72729.122 1.0016.70 c c
ATOM 8457 C ILEI217 9.314 8.16829.609 1.0016.73 c c
ATOM 8458 O ILEI217 9.247 7.931 28.398 1.0016.80 c o
ATOM 8459 N GLUI218 9.885 7.339 30.478 1.0017.02 c N
ATOM 8460 CA GLUI218 10.485 6.09030.031 1.0017.70 c c
ATOM 8461 CB GLUI218 11.172 5.37631.197 1.0018.20 c c
ATOM 8462 CG GLUI218 12.289 6.178 31.844 1.0021.31 c c
ATOM 8463 CD GLUI218 12.951 5.437 32.989 1.0025.72 c c
ATOM 8464 OE1 GLU I 218 13.884 5.998 33.602 1.0026.96 c o
ATOM 8465 OE2 GLU I 218 12.538 4.29433.277 1.0027.07 c o
ATOM 8466 C GLU I 218 9.419 5.19229.418 1.0017.29 c c
ATOM 8467 O GLU I 218 9.642 4.555 28.387 1.0017.62 c o
ATOM 8468 N TH I219 8.253 5.15630.055 1.0016.62 c N
ATOM 8469 CA TH I219 7.146 4.34229.577 1.0015.95 c c
ATOM 8470 CB TH I219 5.952 4.387 30.547 1.0015.95 c c
ATOM 8471 OG1 TH I219 6.356 3.89431.831 1.0015.63 c o
ATOM 8472 CG2 THRI219 4.806 3.53630.021 1.0015.97 c c
ATOM 8473 C THRI219 6.696 4.82528.207 1.0015.64 c c
ATOM 8474 O THRI219 6.414 4.02227.321 1.0015.93 c o
ATOM 8475 N VALI220 6.639 6.141 28.037 1.0014.98 c N
ATOM 8476 CA VALI220 6.235 6.72026.764 1.0014.51 c c
ATOM 8477 CB VALI220 6.143 8.25426.844 1.0014.29 c c
ATOM 8478 CGI VAL I 220 5.716 8.83025.502 1.0014.24 c c
ATOM 8479 CG2 VAL I 220 5.176 8.671 27.942 1.0014.10 c c
ATOM 8480 C VAL I 220 7.233 6.33425.682 1.0014.64 c c
ATOM 8481 O VAL I 220 6.850 5.99224.560 1.0014.79 c o
ATOM 8482 N ILEI221 8.516 6.37526.028 1.0014.43 C N
ATOM 8483 CA ILEI221 9.556 6.01325.075 1.0014.36 c c
ATOM 8484 CB ILEI221 10.962 6.23525.661 1.0014.03 c c
ATOM 8485 CGI ILEI221 11.156 7.70426.041 1.0013.72 c c
ATOM 8486 CD1 ILEI221 11.011 8.66024.877 1.0014.17 c c
ATOM 8487 CG2ILEI221 12.027 5.791 24.671 1.0013.91 c c
ATOM 8488 C ILEI221 9.404 4.55224.672 1.0014.82 c c
ATOM 8489 O ILEI221 9.531 4.20423.496 1.0014.82 c o
ATOM 8490 N GLU I 222 9.112 3.703 25.652 1.0015.51 c N
ATOM 8491 CA GLU I 222 8.936 2.281 25.392 1.0016.52 c c
ATOM 8492 CB GLU I 222 8.730 1.51726.701 1.0016.80 c c
ATOM 8493 CG GLU I 222 9.889 1.63527.677 1.0019.14 c c
ATOM 8494 CD GLU I 222 9.653 0.861 28.959 1.0022.62 c c
ATOM 8495 OE1 GLU I 222 10.539 0.88229.840 1.0024.35 c o
ATOM 8496 OE2 GLU I 222 8.583 0.23029.086 1.0023.98 c o
ATOM 8497 C GLU I 222 7.750 2.06424.464 1.0016.65 c c
ATOM 8498 O GLU I 222 7.802 1.238 23.553 1.0016.95 c o
ATOM 8499 N PHEI223 6.681 2.81724.701 1.0016.70 c N
ATOM 8500 CA PHEI223 5.482 2.71723.885 1.0016.95 c c
ATOM 8501 CB PHEI223 4.370 3.60024.453 1.0016.85 c c
ATOM 8502 CG PHEI223 3.058 3.46023.736 1.0017.23 c c
ATOM 8503 CD1 PHE I 223 2.127 2.51924.145 1.0017.98 c c
ATOM 8504 CE1 PHE I 223 0.919 2.38723.488 1.0018.28 c c
ATOM 8505 CZ PHE I 223 0.629 3.19922.409 1.0018.19 c c ATOM 8506 CE2 PHE I 223 1.548 4.140 21.991 1.00 18.14 C C
ATOM 8507 CD2 PHE I 223 2.755 4.267 22.653 1.00 17.75 C C
ATOM 8508 C PHE 1 223 5.790 3.119 22.450 1.00 17.28 C C
ATOM 8509 O PHE 1 223 5.324 2.482 21.506 1.00 17.17 C O
ATOM 8510 N GLN 1 224 6.581 4.175 22.287 1.00 17.62 C N
ATOM 8511 CA GLN 1 224 6.954 4.619 20.952 1.00 18.16 C C
ATOM 8512 CB GLN 1 224 7.759 5.918 21.021 1.00 18.51 C C
ATOM 8513 CG GLN 1 224 7.015 7.075 21.669 1.00 20.06 C C
ATOM 8514 CD GLN 1 224 7.842 8.344 21.718 1.00 22.03 C C
ATOM 8515 OE1 GLN 1 224 7.387 9.376 22.214 1.00 22.15 C O
ATOM 8516 NE2 GLN I 224 9.064 8.275 21.203 1.00 22.11 C N
ATOM 8517 C GLN 1 224 7.767 3.532 20.261 1.00 18.04 C C
ATOM 8518 O GLN 1 224 7.561 3.238 19.083 1.00 18.17 C O
ATOM 8519 N GLN 1 225 8.688 2.933 21.009 1.00 17.90 C N
ATOM 8520 CA GLN 1 225 9.508 1.840 20.500 1.00 17.95 C C
ATOM 8521 CB GLN 1 225 10.599 1.474 21.509 1.00 18.13 C C
ATOM 8522 CG GLN 1 225 11.551 2.613 21.833 1.00 19.04 C C
ATOM 8523 CD GLN 1 225 12.619 2.213 22.831 1.00 21.22 C C
ATOM 8524 OE1 GLN 1 225 12.659 1.072 23.292 1.00 22.55 C O
ATOM 8525 NE2 GLN 1 225 13.493 3.154 23.172 1.00 22.48 C N
ATOM 8526 C GLN 1 225 8.664 0.611 20.172 1.00 17.84 C C
ATOM 8527 O GLN 1 225 8.892 -0.068 19.171 1.00 17.71 C O
ATOM 8528 N LYS 1 226 7.693 0.334 21.036 1.00 17.95 C N
ATOM 8529 CA LYS 1 226 6.848 -0.831 20.912 1.00 18.00 C C
ATOM 8530 CB LYS 1 226 6.821 -1.593 22.234 1.00 18.21 C C
ATOM 8531 CG LYS 1 226 8.189 -1.697 22.905 1.00 18.50 C C
ATOM 8532 CD LYS 1 226 8.132 -2.591 24.132 1.00 19.87 C C
ATOM 8533 CE LYS 1 226 9.357 -2.411 25.004 1.00 21.36 C C
ATOM 8534 NZ LYS 1 226 9.268 -3.230 26.248 1.00 21.83 C N
ATOM 8535 C LYS 1 226 5.446 -0.408 20.499 1.00 17.84 C C
ATOM 8536 O LYS 1 226 4.672 -1.220 19.998 1.00 17.94 C O
ATOM 8537 N ASN 1 227 5.209 0.900 20.514 1.00 17.70 C N
ATOM 8538 CA ASN 1 227 4.173 1.494 19.683 1.00 17.66 C C
ATOM 8539 CB ASN 1 227 3.153 2.256 20.549 1.00 17.36 C C
ATOM 8540 CG ASN 1 227 2.612 1.411 21.710 1.00 17.40 C C
ATOM 8541 OD1 ASN 1 227 2.451 0.196 21.589 1.00 17.84 C O
ATOM 8542 ND2 ASN I 227 2.333 2.059 22.834 1.00 17.22 C N
ATOM 8543 C ASN 1 227 4.713 2.343 18.506 1.00 17.76 C C
ATOM 8544 O ASN 1 227 3.943 2.750 17.635 1.00 17.92 C O
ATOM 8545 N ASN 1 228 6.045 2.460 18.398 1.00 17.78 C N
ATOM 8546 CA ASN 1 228 6.734 2.532 17.084 1.00 17.59 C C
ATOM 8547 CB ASN 1 228 8.170 3.085 17.155 1.00 17.89 C C
ATOM 8548 CG ASN 1 228 8.870 3.082 15.779 1.00 18.43 C C
ATOM 8549 OD1 ASN 1 228 9.451 2.077 15.366 1.00 18.74 C O
ATOM 8550 ND2 ASN I 228 8.682 4.157 15.022 1.00 18.61 C N
ATOM 8551 C ASN 1 228 6.765 1.204 16.358 1.00 17.09 C C
ATOM 8552 O ASN 1 228 6.004 0.992 15.417 1.00 17.17 C O
ATOM 8553 N A G 1 229 7.685 0.328 16.745 1.00 16.33 C N
ATOM 8554 CA ARG 1 229 7.664 -1.016 16.195 1.00 15.76 C C
ATOM 8555 CB ARG 1 229 8.624 -1.952 16.933 1.00 15.70 C C
ATOM 8556 CG ARG 1 229 9.369 -2.904 16.000 1.00 14.99 C C
ATOM 8557 CD ARG 1 229 9.887 -4.135 16.728 1.00 15.33 C C
ATOM 8558 NE ARG 1 229 9.601 -5.376 16.008 1.00 15.59 C N
ATOM 8559 CZ ARG 1 229 9.926 -6.587 16.451 1.00 15.85 C C
ATOM 8560 NH1 ARG 1 229 10.559 -6.725 17.609 1.00 16.20 C N
ATOM 8561 NH2 ARG 1 229 9.650 -7.660 15.722 1.00 16.63 C N
ATOM 8562 C ARG 1 229 6.238 -1.559 16.223 1.00 15.62 C C
ATOM 8563 O ARG 1 229 5.666 -1.860 15.175 1.00 15.73 C O
ATOM 8564 N LEU 1 230 5.601 -1.468 17.387 1.00 15.46 C N
ATOM 8565 CA LEU 1 230 4.191 -1.829 17.511 1.00 15.22 C C ATOM 8566 CB LEU I 230 3.735 -1.792 18.974 1.00 15.08 C c
ATOM 8567 CG LEU I 230 2.252 -2.079 19.224 1.00 14.70 c c
ATOM 8568 CD1 LEU I 230 2.003 -3.572 19.359 1.00 15.19 c c
ATOM 8569 CD2 LEU I 230 1.743 -1.335 20.449 1.00 15.46 c c
ATOM 8570 C LEU I 230 3.302 - 0.931 16.655 1.00 15.31 c c
ATOM 8571 O LEU I 230 2.417 - 1.415 15.950 1.00 15.46 c o
ATOM 8572 N LEU I 231 3.519 0.377 16.745 1.00 15.48 c N
ATOM 8573 CA LEU I 231 2.678 1.338 16.038 1.00 15.75 c c
ATOM 8574 CB LEU I 231 3.187 2.763 16.257 1.00 15.90 c c
ATOM 8575 CG LEU I 231 2.906 3.379 17.628 1.00 16.63 c c
ATOM 8576 CD1 LEU I 231 3.382 4.819 17.676 1.00 18.45 c c
ATOM 8577 CD2 LEU I 231 1.425 3.292 17.961 1.00 16.67 c c
ATOM 8578 C LEU I 231 2.653 1.025 14.551 1.00 15.76 c c
ATOM 8579 O LEU I 231 1.606 1.092 13.908 1.00 15.84 c o
ATOM 8580 N GLU I 232 3.828 0.750 13.997 1.00 15.71 c N
ATOM 8581 CA GLU I 232 3.973 0.563 12.562 1.00 15.93 c c
ATOM 8582 CB GLU I 232 5.447 0.626 12.163 1.00 16.15 c c
ATOM 8583 CG GLU I 232 6.142 1.913 12.568 1.00 18.59 c c
ATOM 8584 CD GLU I 232 6.407 2.823 11.387 1.00 21.47 c c
ATOM 8585 OE1 GLU I 232 5.892 2.532 10.286 1.00 22.14 c o
ATOM 8586 OE2 GLU I 232 7.214 3.765 11.530 1.00 23.34 c o
ATOM 8587 C GLU I 232 3.377 - ■0.767 12.124 1.00 15.45 c c
ATOM 8588 O GLU I 232 2.921 ■ -0.908 10.990 1.00 15.95 c o
ATOM 8589 N ILE I 233 3.432 -1.757 13.007 1.00 14.54 C N
ATOM 8590 CA ILE I 233 2.713 - 3.000 12.776 1.00 13.69 c c
ATOM 8591 CB ILE I 233 2.998 - 4.028 13.873 1.00 13.63 c c
ATOM 8592 CGI ILE I 233 4.500 -4.093 14.151 1.00 13.58 c c
ATOM 8593 CD1 ILE I 233 4.854 -4.786 15.444 1.00 13.55 c c
ATOM 8594 CG2 ILE I 233 2.458 -5.392 13.469 1.00 13.88 c c
ATOM 8595 C ILE I 233 1.219 -2.728 12.735 1.00 13.28 c c
ATOM 8596 O ILE I 233 0.528 -3.137 11.802 1.00 13.04 C 1 □
ATOM 8597 N TH I 234 0.764 - ■1.898 13.667 1.00 13.18 c N
ATOM 8598 CA TH I 234 -0.651 -1.590 13.796 1.00 13.39 c c
ATOM 8599 CB TH I 234 -0.913 -0.636 14.974 1.00 13.21 c c
ATOM 8600 OG1 THR I 234 -0.476 -1.248 16.193 1.00 13.15 c : o
ATOM 8601 CG2 THR I 234 -2.395 -0.311 15.078 1.00 13.22 c c
ATOM 8602 C THR I 234 -1.208 - ■0.981 12.514 1.00 13.76 c c
ATOM 8603 O THR I 234 -2.230■ -1.432 11.997 1.00 13.95 c o
ATOM 8604 N ARG I 235 -0.535 0.045 12.003 1.00 14.26 c N
ATOM 8605 CA ARG I 235 -0.945 0.670 10.752 1.00 14.92 c c
ATOM 8606 CB ARG I 235 -0.051 1.874 10.432 1.00 15.30 c c
ATOM 8607 CG ARG I 235 0.875 1.681 9.240 1.00 16.27 c c
ATOM 8608 CD ARG I 235 2.190 2.436 9.413 1.00 18.52 c c
ATOM 8609 NE ARG I 235 2.083 3.558 10.344 1.00 17.86 c N
ATOM 8610 CZ ARG I 235 1.516 4.724 10.051 1.00 16.91 c c
ATOM 8611 NH1 ARG I 235 0.855 1 4.874 8.912 1.00 16.59 c N
ATOM 8612 NH2 ARG I 235 1.511 5.703 10.946 1.00 16.86 c N
ATOM 8613 C ARG I 235 -0.904 -0.353 9.620 1.00 15.05 c c
ATOM 8614 O ARG I 235 -1.939 -0.693 9.045 1.00 15.15 c o
ATOM 8615 N GLU I 236 0.240■ -1.020 9.504 1.00 15.18 c N
ATOM 8616 CA GLU I 236 0.451 -2.047 8.490 1.00 15.24 c c
ATOM 8617 CB GLU I 236 1.725 -2.835 8.801 1.00 15.69 c c
ATOM 8618 CG GLU I 236 2.432 -3.396 7.580 1.00 18.22 c c
ATOM 8619 CD GLU I 236 3.760 -4.040 7.926 1.00 21.59 c c
ATOM 8620 OE1 GLU I 236 4.381 -4.645 7.027 1.00 24.41 c o
ATOM 8621 OE2 GLU I 236 4.182 -3.944 9.097 1.00 21.59 c o
ATOM 8622 C GLU I 236 -0.735 ■ -2.999 8.400 1.00 14.61 c c
ATOM 8623 O GLU I 236 -1.191 -3.334 7.307 1.00 14.82 c o
ATOM 8624 N PHE I 237 -1.184 - 3.485 9.552 1.00 14.05 c N
ATOM 8625 CA PHE I 237 -2.318 -4.397 9.602 1.00 13.84 c c ATOM 8626 CB PHE 1 237 -2.466 -4.996 11.003 1.00 14.04 C C
ATOM 8627 CG PHE 1 237 -1.643 -6.235 11.225 1.00 14.84 C C
ATOM 8628 CD1 PHE I 237 -0.734 -6.296 12.267 1.00 15.30 C C
ATOM 8629 CE1 PHE I 237 -0.006 -7.446 12.503 1.00 15.15 C C
ATOM 8630 CZ PHE 1 237 -0.197 -8.557 11.708 1.00 15.19 C C
ATOM 8631 CE2 PHE I 237 -1.110 -8.514 10.673 1.00 15.02 C C
ATOM 8632 CD2 PHE I 237 -1.831 -7.360 10.439 1.00 15.03 C C
ATOM 8633 C PHE 1 237 -3.607 -3.689 9.195 1.00 13.51 C C
ATOM 8634 O PHE 1 237 -4.387 -4.213 8.399 1.00 13.43 C O
ATOM 8635 N SE I 238 -3.830 -2.503 9.754 1.00 13.11 C N
ATOM 8636 CA SE I 238 -5.032 -1.729 9.460 1.00 12.82 C C
ATOM 8637 CB SE I 238 -5.049 -0.438 10.279 1.00 12.86 C C
ATOM 8638 OG SE 1 238 -5.205 -0.711 11.660 1.00 12.76 C O
ATOM 8639 C SER 1 238 -5.104 -1.400 7.977 1.00 12.69 C C
ATOM 8640 O SER 1 238 -6.187 -1.237 7.414 1.00 12.63 C O
ATOM 8641 N VAL 1 239 -3.937 -1.313 7.349 1.00 12.59 C N
ATOM 8642 CA VAL 1 239 -3.858 -1.042 5.923 1.00 12.80 C C
ATOM 8643 CB VAL 1 239 -2.482 -0.473 5.524 1.00 12.71 C C
ATOM 8644 CGI VAL 1 239 -2.390 -0.321 4.012 1.00 13.63 C C
ATOM 8645 CG2 VAL 1 239 -2.239 0.859 6.214 1.00 13.57 C C
ATOM 8646 C VAL 1 239 -4.144 -2.286 5.090 1.00 12.94 C C
ATOM 8647 O VAL 1 239 -4.320 -2.190 3.877 1.00 13.10 C O
ATOM 8648 N ASN 1 240 -4.139 -3.458 5.721 1.00 4.15 C N
ATOM 8649 CA ASN 1 240 -4.166 -4.709 4.966 1.00 4.33 C C
ATOM 8650 CB ASN 1 240 -2.941 -5.569 5.281 1.00 4.59 C C
ATOM 8651 CG ASN 1 240 -1.674 -5.027 4.647 1.00 5.36 C C
ATOM 8652 OD1 ASN 1 240 -1.524 -5.043 3.423 1.00 6.27 C O
ATOM 8653 ND2 ASN I 240 -0.816 -4.427 5.465 1.00 7.15 C N
ATOM 8654 C ASN 1 240 -5.454 -5.529 5.074 1.00 4.19 C C
ATOM 8655 O ASN 1 240 -5.634 -6.507 4.347 1.00 4.19 C O
ATOM 8656 N ALA 1 241 -6.385 -5.073 5.904 1.00 3.93 C N
ATOM 8657 CA ALA 1 241 -7.593 -5.840 6.186 1.00 3.90 C C
ATOM 8658 CB ALA 1 241 -8.563 -5.749 5.020 1.00 3.86 C C
ATOM 8659 C ALA 1 241 -7.253 -7.297 6.491 1.00 4.22 C C
ATOM 8660 O ALA 1 241 -7.778 -8.212 5.856 1.00 4.47 C O
ATOM 8661 N GLY 1 242 -6.289 -7.497 7.386 1.00 4.53 C N
ATOM 8662 CA GLY 1 242 -6.124 -8.774 8.078 1.00 4.65 C C
ATOM 8663 C GLY 1 242 -5.398 -9.848 7.282 1.00 4.67 C C
ATOM 8664 O GLY 1 242 -5.496 -11.034 7.600 1.00 5.27 C O
ATOM 8665 N VAL 1 243 -4.611 -9.433 6.292 1.00 4.37 C N
ATOM 8666 CA VAL 1 243 -3.780 -10.366 5.531 1.00 4.32 C C
ATOM 8667 CB VAL 1 243 -4.570 -11.042 4.389 1.00 3.99 C C
ATOM 8668 CGI VAL 1 243 -3.987 -12.411 4.078 1.00 4.22 C C
ATOM 8669 CG2 VAL 1 243 -6.042 -11.154 4.748 1.00 3.85 C C
ATOM 8670 C VAL 1 243 -2.571 -9.658 4.932 1.00 4.61 C C
ATOM 8671 O VAL 1 243 -2.704 -8.607 4.308 1.00 4.89 C O
ATOM 8672 N THR 1 244 -1.402 -10.269 5.072 1.00 4.95 C N
ATOM 8673 CA THR 1 244 -0.168 -9.654 4.604 1.00 5.71 C C
ATOM 8674 CB THR 1 244 0.678 -9.128 5.775 1.00 6.11 C C
ATOM 8675 OG1 THR I 244 -0.078 -9.209 6.989 1.00 7.17 C O
ATOM 8676 CG2 THR 1 244 1.091 -7.686 5.532 1.00 7.55 C C
ATOM 8677 C THR 1 244 0.664 -10.649 3.813 1.00 5.61 C C
ATOM 8678 O THR 1 244 0.811 -11.803 4.214 1.00 5.85 C O
ATOM 8679 N THR 1 245 1.346 -10.150 2.791 1.00 5.53 C N
ATOM 8680 CA THR 1 245 2.556 -10.791 2.308 1.00 5.81 C C
ATOM 8681 CB THR 1 245 2.426 -11.170 0.818 1.00 6.13 C C
ATOM 8682 OG1 THR 1 245 1.421 -12.181 0.668 1.00 8.11 C O
ATOM 8683 CG2 THR 1 245 3.746 -11.696 0.281 1.00 6.63 C C
ATOM 8684 C THR 1 245 3.748 -9.865 2.542 1.00 5.73 C C
ATOM 8685 O THR 1 245 3.568 -8.705 2.916 1.00 5.86 C O ATOM 8686 N PRO I 246 4.963 -10.337 2.223 1.00 5.68 C N
ATOM 8687 CA PRO I 246 5.942 -10.579 3.269 1.00 5.11 c c
ATOM 8688 CB PRO I 246 6.802 -9.317 3.210 1.00 5.19 c c
ATOM 8689 CG PRO I 246 6.717 -8.878 1.734 1.00 5.90 c c
ATOM 8690 CD PRO I 246 5.613 -9.691 1.074 1.00 6.36 c c
ATOM 8691 C PRO I 246 5.360 -10.786 4.664 1.00 4.85 c c
ATOM 8692 O PRO I 246 4.465 -10.053 5.084 1.00 5.25 c o
ATOM 8693 N VAL I 247 5.795 -11.859 5.316 1.00 4.35 c N
ATOM 8694 CA VAL I 247 5.555 -12.048 6.739 1.00 3.82 c c
ATOM 8695 CB VAL I 247 5.603 -13.536 7.127 1.00 3.52 c c
ATOM 8696 CGI VAL I 247 5.206 -13.717 8.584 1.00 3.62 c c
ATOM 8697 CG2 VAL I 247 4.694 -14.347 6.218 1.00 3.60 c c
ATOM 8698 C VAL I 247 6.576 -11.271 7.558 1.00 3.69 c c
ATOM 8699 O VAL I 247 7.744 -11.653 7.641 1.00 3.36 c o
ATOM 8700 N SER I 248 6.172 -10.077 7.973 1.00 3.72 c N
ATOM 8701 CA SER I 248 7.077 -9.138 8.611 1.00 3.96 c c
ATOM 8702 CB SER I 248 6.291 -7.973 9.214 1.00 4.07 c c
ATOM 8703 OG SER I 248 5.661 -8.356 10.425 1.00 4.13 c o
ATOM 8704 C SER I 248 7.885 -9.830 9.695 1.00 4.35 c c
ATOM 8705 O SER I 248 7.453 -10.838 10.257 1.00 4.36 c o
ATOM 8706 N THR I 249 9.008 -9.223 10.057 1.00 4.53 c N
ATOM 8707 CA THR I 249 9.752 -9.638 11.235 1.00 4.61 c c
ATOM 8708 CB THR I 249 11.104 -8.916 11.329 1.00 4.70 c c
ATOM 8709 OG1 THR I 249 10.889 -7.544 11.679 1.00 5.42 c : o
ATOM 8710 CG2 THR I 249 11.833 -8.984 9.999 1.00 4.88 c c
ATOM 8711 C THR I 249 8.955 -9.383 12.509 1.00 4.47 c c
ATOM 8712 O THR I 249 9.321 -9.861 13.584 1.00 4.74 c o
ATOM 8713 N TYR I 250 7.864 -8.633 12.388 1.00 4.32 c N
ATOM 8714 CA TYR I 250 6.956 -8.435 13.512 1.00 4.42 c c
ATOM 8715 CB TYR I 250 6.195 -7.113 13.381 1.00 4.91 c c
ATOM 8716 CG TYR I 250 7.072 -5.881 13.272 1.00 6.81 c c
ATOM 8717 CD1 TYR I 250 6.791 -4.897 12.333 1.00 8.89 c c
ATOM 8718 CE1 TYR I 250 7.556 -3.752 12.243 1.00 10.73 c c
ATOM 8719 CZ TYR I 250 8.587 -3.549 13.137 1.00 12.28 c c
ATOM 8720 OH TYR I 250 9.370 -2.421 13.032 1.00 12.24 c o
ATOM 8721 CE2 TYR I 250 8.851 -4.483 14.121 1.00 12.15 c c
ATOM 8722 CD2 TYR I 250 8.067 -5.621 14.209 1.00 9.81 c c
ATOM 8723 C TYR I 250 5.973 -9.592 13.662 1.00 4.21 c c
ATOM 8724 O TYR I 250 5.525 -9.893 14.768 1.00 4.20 c o
ATOM 8725 N MET I 251 5.574 -10.183 12.541 1.00 4.14 c N
ATOM 8726 CA MET I 251 4.731 -11.372 12.574 1.00 4.15 c c
ATOM 8727 CB MET I 251 4.160 -11.662 11.187 1.00 4.14 c c
ATOM 8728 CG MET I 251 3.297 -10.547 10.630 1.00 4.51 c c
ATOM 8729 SD MET I 251 1.731 -10.386 11.505 1.00 3.81 c s
ATOM 8730 CE MET I 251 0.800 -9.412 10.327 1.00 4.55 c c
ATOM 8731 C MET I 251 5.540 -12.565 13.057 1.00 4.13 c c
ATOM 8732 O MET I 251 5.127 -13.289 13.964 1.00 4.24 c o
ATOM 8733 N LEU I 252 6.728 -12.718 12.487 1.00 4.23 c N
ATOM 8734 CA LEU I 252 7.586 -13.848 12.792 1.00 4.22 c c
ATOM 8735 CB LEU I 252 7.586 -14.839 11.631 1.00 4.14 c c
ATOM 8736 CG LEU I 252 6.703 -16.071 11.816 1.00 4.05 c c
ATOM 8737 CD1 LEU I 252 7.171 -17.204 10.918 1.00 5.22 c c
ATOM 8738 CD2 LEU I 252 6.692 -16.508 13.273 1.00 6.20 c c
ATOM 8739 C LEU I 252 8.998 -13.356 13.040 1.00 4.62 c c
ATOM 8740 O LEU I 252 9.599 -12.712 12.182 1.00 4.97 c o
ATOM 8741 N THR I 253 9.531 -13.670 14.212 1.00 4.90 c N
ATOM 8742 CA THR I 253 10.942 -13.463 14.472 1.00 5.57 c c
ATOM 8743 CB THR I 253 11.265 -13.708 15.946 1.00 5.55 c c
ATOM 8744 OG1 THR I 253 10.337 -12.987 16.765 1.00 6.43 C O ATOM 8745 CG2 THR I 253 12.673 -13.251 16.259 1.00 6.28 C C ATOM 8746 C TH I 253 11.753 -14.424 13.622 1.00 6.03 C c
ATOM 8747 O TH I 253 11.315 -15.541 13.349 1.00 6.68 c o
ATOM 8748 N ASN I 254 12.961 -14.015 13.255 1.00 6.39 c N
ATOM 8749 CA ASN I 254 13.951 -14.973 12.800 1.00 6.79 c c
ATOM 8750 CB ASN I 254 15.341 -14.348 12.762 1.00 6.85 c c
ATOM 8751 CG ASN I 254 16.324 -15.177 11.964 1.00 6.81 c c
ATOM 8752 OD1 ASN I 254 16.152 -15.366 10.760 1.00 7.67 c : o
ATOM 8753 ND2 ASN I 254 17.271 -15.799 12.657 1.00 6.19 c : N
ATOM 8754 C ASN I 254 13.964 -16.211 13.686 1.00 7.08 c c
ATOM 8755 O ASN I 254 13.654 -17.312 13.231 1.00 6.90 c o
ATOM 8756 N SE I 255 14.283 -16.017 14.962 1.00 7.21 c N
ATOM 8757 CA SE I 255 14.292 -17.112 15.929 1.00 7.37 c c
ATOM 8758 CB SER I 255 14.338 -16.568 17.360 1.00 8.09 c c
ATOM 8759 OG SER I 255 14.953 -15.293 17.407 1.00 10.47 c o
ATOM 8760 C SER I 255 13.078 -18.024 15.750 1.00 6.82 c c
ATOM 8761 O SER I 255 13.205 -19.249 15.768 1.00 6.99 c o
ATOM 8762 N GLU I 256 11.901 -17.422 15.611 1.00 6.17 c N
ATOM 8763 CA GLU I 256 10.658 -18.184 15.544 1.00 6.13 c c
ATOM 8764 CB GLU I 256 9.452 -17.266 15.742 1.00 6.22 c c
ATOM 8765 CG GLU I 256 9.210 -16.863 17.185 1.00 8.41 c c
ATOM 8766 CD GLU I 256 8.527 -15.516 17.299 1.00 10.26 c c
ATOM 8767 OE1 GLU I 256 8.232 -14.907 16.248 1.00 11.90 c o
ATOM 8768 OE2 GLU I 256 8.275 -15.070 18.437 1.00 9.55 c o
ATOM 8769 C GLU I 256 10.535 -18.895 14.209 1.00 5.76 c c
ATOM 8770 O GLU I 256 10.154 -20.064 14.154 1.00 5.93 c o
ATOM 8771 N LEU I 257 10.669 -18.124 13.134 1.00 5.67 c N
ATOM 8772 CA LEU I 257 10.638 -18.679 11.787 1.00 5.37 c c
ATOM 8773 CB LEU I 257 11.010 -17.613 10.753 1.00 5.03 c c
ATOM 8774 CG LEU I 257 11.316 -18.130 9.344 1.00 3.65 c c
ATOM 8775 CD1 LEU I 257 10.067 -18.702 8.689 1.00 2.00 c c
ATOM 8776 CD2 LEU I 257 11.917 -17.030 8.485 1.00 2.14 c c
ATOM 8777 C LEU I 257 11.580 -19.871 11.670 1.00 5.64 c c
ATOM 8778 O LEU I 257 11.234 -20.895 11.079 1.00 5.81 c o
ATOM 8779 N LEU I 258 12.764 -19.741 12.259 1.00 5.75 c N
ATOM 8780 CA LEU I 258 13.808 -20.739 12.081 1.00 5.91 c c
ATOM 8781 CB LEU I 258 15.156 -20.215 12.583 1.00 6.10 c c
ATOM 8782 CG LEU I 258 16.059 -19.626 11.495 1.00 5.75 c c
ATOM 8783 CD1 LEU I 258 17.208 -18.836 12.101 1.00 6.33 c c
ATOM 8784 CD2 LEU I 258 16.577 -20.724 10.577 1.00 7.33 c c
ATOM 8785 C LEU I 258 13.464 -22.074 12.736 1.00 6.03 c c
ATOM 8786 O LEU I 258 13.589 -23.125 12.109 1.00 5.73 c o
ATOM 8787 N SER I 259 12.980 -22.030 13.974 1.00 6.47 c N
ATOM 8788 CA SER I 259 12.538 -23.243 14.662 1.00 6.95 c c
ATOM 8789 CB SER I 259 12.400 -23.000 16.168 1.00 7.05 c c
ATOM 8790 OG SER I 259 11.147 -23.460 16.650 1.00 6.86 c o
ATOM 8791 C SER I 259 11.220 -23.759 14.097 1.00 6.74 c c
ATOM 8792 O SER I 259 10.905 -24.943 14.213 1.00 6.86 c o
ATOM 8793 N LEU I 260 10.411 -22.844 13.576 1.00 6.31 c N
ATOM 8794 CA LEU I 260 9.188 -23.211 12.880 1.00 6.09 c c
ATOM 8795 CB LEU I 260 8.407 -21.957 12.484 1.00 6.09 c c
ATOM 8796 CG LEU I 260 7.140 -21.665 13.291 1.00 6.24 c c
ATOM 8797 CD1 LEU I 260 6.291 -20.595 12.611 1.00 6.53 c c
ATOM 8798 CD2 LEU I 260 6.337 -22.944 13.521 1.00 5.98 c c
ATOM 8799 C LEU I 260 9.497 -24.047 11.644 1.00 6.25 c c
ATOM 8800 O LEU I 260 8.809 -25.028 11.361 1.00 6.37 c o
ATOM 8801 N ILE I 261 10.452 -23.580 10.847 1.00 6.63 c N
ATOM 8802 CA ILE I 261 10.952 -24.360 9.723 1.00 7.19 c c
ATOM 8803 CB ILE I 261 12.165 -23.681 9.061 1.00 7.09 c c
ATOM 8804 CGI ILE I 261 11.703 -22.635 8.046 1.00 7.46 c c
ATOM 8805 CD1 ILE I 261 12.646 -21.460 7.909 1.00 8.38 c c ATOM 8806 CG2 ILE I 261 13.055 -24.718 8.391 1.00 6.61 C c
ATOM 8807 C ILE I 261 11.389 -25.723 10.228 1.00 8.01 c c
ATOM 8808 O ILE I 261 10.967 -26.758 9.713 1.00 8.26 c o
ATOM 8809 N ASN I 262 12.206 -25.708 11.273 1.00 9.05 c N
ATOM 8810 CA ASN I 262 12.640 -26.935 11.912 1.00 9.88 c c
ATOM 8811 CB ASN I 262 13.220 -26.636 13.292 1.00 9.99 c c
ATOM 8812 CG ASN I 262 14.327 -27.590 13.672 1.00 11.16 c c
ATOM 8813 OD1 ASN I 262 14.709 -28.457 12.886 1.00 12.70 C O
ATOM 8814 ND2 ASN I 262 14.912 -27.379 14.844 1.00 13.20 C N
ATOM 8815 C ASN I 262 11.500 -27.939 12.023 1.00 10.17 c c
ATOM 8816 O ASN I 262 11.661 -29.108 11.675 1.00 10.52 c o
ATOM 8817 N ASP I 263 10.315 -27.444 12.368 1.00 10.62 c N
ATOM 8818 CA ASP I 263 9.203 -28.311 12.741 1.00 11.02 c c
ATOM 8819 CB ASP I 263 8.230 -27.584 13.675 1.00 11.49 c c
ATOM 8820 CG ASP I 263 7.026 -28.435 14.040 1.00 12.80 c c
ATOM 8821 OD1 ASP I 263 7.219 -29.586 14.487 1.00 14.72 c o
ATOM 8822 OD2 ASP I 263 5.886 -27.978 13.811 1.00 13.88 c o
ATOM 8823 C ASP I 263 8.460 -28.855 11.520 1.00 10.92 c c
ATOM 8824 O ASP I 263 7.619 -29.748 11.642 1.00 10.96 c o
ATOM 8825 N MET I 264 8.807 -28.346 10.341 1.00 10.91 c N
ATOM 8826 CA MET I 264 8.105 -28.707 9.110 1.00 10.78 c c
ATOM 8827 CB MET I 264 8.397 -27.687 8.007 1.00 10.51 c c
ATOM 8828 CG MET I 264 7.934 -26.276 8.329 1.00 11.26 c c
ATOM 8829 SD MET I 264 8.142 -25.144 6.942 1.00 12.70 c s
ATOM 8830 CE MET I 264 9.799 -25.565 6.411 1.00 13.92 c c
ATOM 8831 C MET I 264 8.466 -30.116 8.631 1.00 10.85 c c
ATOM 8832 O MET I 264 9.644 -30.472 8.578 1.00 11.03 c o
ATOM 8833 N PRO I 265 7.451 -30.900 8.230 1.00 10.88 c N
ATOM 8834 CA PRO I 265 7.647 -32.293 7.841 1.00 11.09 c c
ATOM 8835 CB PRO I 265 6.215 -32.820 7.685 1.00 11.28 c c
ATOM 8836 CG PRO I 265 5.387 -31.612 7.438 1.00 11.24 c c
ATOM 8837 CD PRO I 265 6.025 -30.534 8.255 1.00 11.03 c c
ATOM 8838 C PRO I 265 8.400 -32.420 6.521 1.00 11.19 c c
ATOM 8839 O PRO I 265 7.889 -33.027 5.580 1.00 11.47 c o
ATOM 8840 N ILE I 266 9.642 -31.940 6.488 1.00 11.54 C N
ATOM 8841 CA ILE I 266 10.448 -31.980 5.266 1.00 12.15 c c
ATOM 8842 CB ILE I 266 10.586 -30.587 4.621 1.00 12.22 c c
ATOM 8843 CGI ILE I 266 11.051 -29.559 5.654 1.00 12.53 c c
ATOM 8844 CD1 ILE I 266 11.557 -28.269 5.047 1.00 12.40 c c
ATOM 8845 CG2 ILE I 266 9.271 -30.157 3.984 1.00 12.74 c c
ATOM 8846 C ILE I 266 11.839 -32.574 5.485 1.00 12.29 c c
ATOM 8847 O ILE I 266 12.291 -32.724 6.619 1.00 12.36 C 0
ATOM 8848 N THR I 267 12.498 -32.936 4.388 1.00 12.29 c N
ATOM 8849 CA THR I 267 13.868 -33.435 4.440 1.00 12.43 c c
ATOM 8850 CB THR I 267 14.386 -33.809 3.039 1.00 12.40 c c
ATOM 8851 OG1 THR I 267 15.460 -32.934 2.674 1.00 13.21 c : o
ATOM 8852 CG2 THR I 267 13.274 -33.699 2.010 1.00 12.21 c c
ATOM 8853 C THR I 267 14.797 -32.391 5.046 1.00 12.37 c c
ATOM 8854 O THR I 267 14.403 -31.244 5.251 1.00 12.29 c o
ATOM 8855 N ASN I 268 16.045 -32.779 5.282 1.00 12.47 c N
ATOM 8856 CA ASN I 268 16.965 -31.945 6.045 1.00 12.57 c c
ATOM 8857 CB ASN I 268 18.041 -32.800 6.715 1.00 12.69 c c
ATOM 8858 CG ASN I 268 17.682 -33.171 8.138 1.00 13.65 c c
ATOM 8859 OD1 ASN I 268 16.611 -32.820 8.631 1.00 14.37 c : o
ATOM 8860 ND2 ASN I 268 18.569 -33.905 8.800 1.00 15.74 c : N
ATOM 8861 C ASN I 268 17.608 -30.843 5.211 1.00 12.43 c c
ATOM 8862 O ASN I 268 17.775 -29.717 5.680 1.00 12.51 c o
ATOM 8863 N ASP I 269 18.038 -31.194 4.005 1.00 12.34 c N
ATOM 8864 CA ASP I 269 18.574 -30.211 3.072 1.00 12.33 c c
ATOM 8865 CB ASP I 269 19.015 -30.891 1.777 1.00 12.89 c c ATOM 8866 CG ASP I 269 20.071 -31.950 2.007 1.00 14.84 C c
ATOM 8867 ODl ASP I 269 21.002 -31.699 2.800 1.00 16.90 c o
ATOM 8868 OD2 ASP I 269 19.952 -33.047 1.422 1.00 17.65 c o
ATOM 8869 C ASP I 269 17.539 -29.138 2.769 1.00 11.60 c c
ATOM 8870 O ASP I 269 17.861 -27.952 2.696 1.00 11.65 c o
ATOM 8871 N GLN I 270 16.295 -29.564 2.585 1.00 10.62 c N
ATOM 8872 CA GLN I 270 15.182 -28.633 2.501 1.00 10.01 c c
ATOM 8873 CB GLN I 270 13.853 -29.384 2.525 1.00 10.18 c c
ATOM 8874 CG GLN I 270 12.845 -28.862 1.525 1.00 11.49 c c
ATOM 8875 CD GLN I 270 12.012 -29.968 0.918 1.00 14.38 c c
ATOM 8876 OE1 GLN I 270 10.789 -29.863 0.836 1.00 16.38 c : o
ATOM 8877 NE2 GLN I 270 12.665 -31.057 0.530 1.00 15.41 c : N
ATOM 8878 C GLN I 270 15.228 -27.620 3.636 1.00 9.48 c c
ATOM 8879 O GLN I 270 15.310 -26.415 3.400 1.00 9.12 c o
ATOM 8880 N LYS I 271 15.170 -28.112 4.868 1.00 9.19 c N
ATOM 8881 CA LYS I 271 15.211 -27.240 6.035 1.00 8.89 c c
ATOM 8882 CB LYS I 271 15.253 -28.064 7.322 1.00 8.52 c c
ATOM 8883 CG LYS I 271 13.948 -28.773 7.643 1.00 9.14 c c
ATOM 8884 CD LYS I 271 13.927 -29.280 9.076 1.00 10.72 c c
ATOM 8885 CE LYS 1 271 13.274 -30.648 9.163 1.00 10.79 c c
ATOM 8886 NZ LYS 1 271 12.712 -30.914 10.514 1.00 9.77 c N
ATOM 8887 C LYS I 271 16.405 -26.295 5.973 1.00 8.83 c c
ATOM 8888 O LYS I 271 16.257 -25.082 6.127 1.00 9.05 c o
ATOM 8889 N LYS I 272 17.583 -26.854 5.707 1.00 8.65 c N
ATOM 8890 CA LYS I 272 18.796 -26.058 5.548 1.00 8.50 c c
ATOM 8891 CB LYS I 272 19.977 -26.948 5.145 1.00 9.14 c c
ATOM 8892 CG LYS I 272 21.158 -26.189 4.547 1.00 11.58 c c
ATOM 8893 CD LYS I 272 22.213 -27.138 3.991 1.00 15.78 c c
ATOM 8894 CE LYS I 272 23.576 -26.464 3.891 1.00 17.65 c c
ATOM 8895 NZ LYS I 272 24.667 -27.446 3.641 1.00 19.68 c N
ATOM 8896 C LYS I 272 18.599 -24.956 4.514 1.00 7.88 c c
ATOM 8897 O LYS I 272 18.919 -23.794 4.761 1.00 8.12 c o
ATOM 8898 N LEU I 273 18.111 -25.336 3.338 1.00 6.95 c N
ATOM 8899 CA LEU I 273 17.867 -24.375 2.271 1.00 5.70 c c
ATOM 8900 CB LEU I 273 17.235 -25.063 1.060 1.00 5.85 c c
ATOM 8901 CG LEU I 273 16.754 -24.131 -0.054 1.00 4.65 c c
ATOM 8902 CD1 LEU I 273 17.928 -23.571 -0.841 1.00 4.57 c c
ATOM 8903 CD2 LEU I 273 15.777 -24.846 -0.972 1.00 3.69 c c
ATOM 8904 C LEU I 273 16.969 -23.244 2.755 1.00 5.14 c c
ATOM 8905 O LEU I 273 17.345 -22.074 2.702 1.00 5.25 c o
ATOM 8906 N MET I 274 15.776 -23.601 3.221 1.00 4.52 c N
ATOM 8907 CA MET I 274 14.828 -22.616 3.723 1.00 4.59 c c
ATOM 8908 CB MET I 274 13.599 -23.308 4.314 1.00 4.35 c c
ATOM 8909 CG MET I 274 12.709 -23.975 3.279 1.00 4.50 c c
ATOM 8910 SD MET I 274 11.194 -24.645 3.989 1.00 5.51 c s
ATOM 8911 CE MET I 274 10.326 -23.138 4.417 1.00 5.26 c c
ATOM 8912 C MET I 274 15.479 -21.720 4.768 1.00 5.18 c c
ATOM 8913 O MET I 274 15.279 -20.505 4.771 1.00 5.61 c o
ATOM 8914 N SE I 275 16.315 -22.319 5.610 1.00 5.89 c N
ATOM 8915 CA SE I 275 16.961 -21.588 6.688 1.00 6.18 c c
ATOM 8916 CB SE I 275 17.607 -22.555 7.682 1.00 6.33 c c
ATOM 8917 OG SE I 275 16.654 -23.470 8.193 1.00 5.91 c o
ATOM 8918 C SER I 275 17.996 -20.603 6.157 1.00 6.58 c c
ATOM 8919 O SER I 275 18.181 -19.526 6.721 1.00 7.03 c o
ATOM 8920 N ASN I 276 18.615 -20.940 5.030 1.00 7.07 c N
ATOM 8921 CA ASN I 276 19.593 -20.050 4.412 1.00 7.86 c c
ATOM 8922 CB ASN I 276 20.696 -20.854 3.711 1.00 8.34 c c
ATOM 8923 CG ASN I 276 21.868 -21.177 4.633 1.00 9.77 c c
ATOM 8924 ODl ASN I 276 22.167 -20.430 5.567 1.00 11.84 c o
ATOM 8925 ND2 ASN I 276 22.557 -22.278 4.349 1.00 11.15 C N ATOM 8926 C ASN I 276 18.976 -19.029 3.453 1.00 7.71 C C
ATOM 8927 O ASN I 276 19.695 -18.349 2.722 1.00 7.84 C O
ATOM 8928 N ASN 1 277 17.655 -18.870 3.509 1.00 7.77 C N
ATOM 8929 CA ASN 1 277 16.938 -18.098 2.491 1.00 7.85 C C
ATOM 8930 CB ASN 1 277 16.575 -18.987 1.304 1.00 7.58 C C
ATOM 8931 CG ASN 1 277 17.725 -19.157 0.335 1.00 8.29 C C
ATOM 8932 OD1 ASN I 277 18.053 -18.240 -0.417 1.00 9.04 C O
ATOM 8933 ND2 ASN I 277 18.427 -20.279 0.443 1.00 9.57 C N
ATOM 8934 C ASN 1 277 15.697 -17.371 3.006 1.00 7.86 C C
ATOM 8935 O ASN 1 277 14.826 -16.977 2.229 1.00 7.85 C O
ATOM 8936 N VAL 1 278 15.593 -17.272 4.328 1.00 7.67 C N
ATOM 8937 CA VAL 1 278 14.554 -16.489 4.998 1.00 7.77 C C
ATOM 8938 CB VAL 1 278 15.120 -15.739 6.215 1.00 7.98 C C
ATOM 8939 CGI VAL 1 278 15.116 -16.638 7.440 1.00 7.21 C C
ATOM 8940 CG2 VAL I 278 16.524 -15.234 5.918 1.00 8.99 C C
ATOM 8941 C VAL 1 278 13.813 -15.497 4.105 1.00 7.76 C C
ATOM 8942 O VAL 1 278 12.583 -15.441 4.123 1.00 7.84 C O
ATOM 8943 N GLN 1 279 14.562 -14.581 3.501 1.00 7.47 C N
ATOM 8944 CA GLN 1 279 13.966 -13.446 2.809 1.00 7.07 C C
ATOM 8945 CB GLN 1 279 15.038 -12.668 2.045 1.00 7.62 C C
ATOM 8946 CG GLN 1 279 14.870 -11.159 2.116 1.00 10.35 C C
ATOM 8947 CD GLN 1 279 15.712 -10.430 1.091 1.00 13.70 C C
ATOM 8948 OE1 GLN 1 279 16.199 -11.027 0.132 1.00 15.06 C O
ATOM 8949 NE2 GLN 1 279 15.865 -9.124 1.275 1.00 13.97 C N
ATOM 8950 C GLN 1 279 12.868 -13.901 1.851 1.00 6.02 C C
ATOM 8951 O GLN 1 279 11.734 -13.423 1.912 1.00 5.45 C O
ATOM 8952 N ILE 1 280 13.249 -14.748 0.901 1.00 5.25 C N
ATOM 8953 CA ILE 1 280 12.304 -15.343 -0.031 1.00 4.74 C C
ATOM 8954 CB ILE 1 280 12.978 -16.451 -0.860 1.00 4.58 C C
ATOM 8955 CGI ILE 1 280 14.333 -15.973 -1.385 1.00 4.16 C C
ATOM 8956 CD 1 ILE I 280 14.238 -15.065 -2.587 1.00 3.88 C C
ATOM 8957 CG2 ILE 1 280 12.065 -16.900 -1.996 1.00 3.92 C C
ATOM 8958 C ILE 1 280 11.122 -15.946 0.716 1.00 4.43 C C
ATOM 8959 O ILE 1 280 9.972 -15.547 0.516 1.00 4.39 C O
ATOM 8960 N VAL I 281 11.409 -16.970 1.513 1.00 4.05 C N
ATOM 8961 CA VAL 1 281 10.390 -17.623 2.319 1.00 3.58 C C
ATOM 8962 CB VAL 1 281 11.010 -18.335 3.534 1.00 3.13 C C
ATOM 8963 CGI VAL 1 281 10.006 -19.291 4.158 1.00 2.34 C C
ATOM 8964 CG2 VAL 1 281 12.277 -19.073 3.127 1.00 2.21 C C
ATOM 8965 C VAL 1 281 9.373 -16.601 2.806 1.00 3.96 C C
ATOM 8966 O VAL 1 281 8.186 -16.694 2.495 1.00 4.15 C O
ATOM 8967 N ARG 1 282 9.857 -15.593 3.522 1.00 4.23 C N
ATOM 8968 CA ARG 1 282 8.995 -14.530 4.016 1.00 4.45 C C
ATOM 8969 CB ARG 1 282 9.829 -13.427 4.656 1.00 3.96 C C
ATOM 8970 CG ARG 1 282 10.637 -13.896 5.841 1.00 2.99 C C
ATOM 8971 CD ARG 1 282 10.550 -12.909 6.979 1.00 2.28 C C
ATOM 8972 NE ARG 1 282 11.505 -13.236 8.029 1.00 2.00 C N
ATOM 8973 CZ ARG 1 282 11.175 -13.463 9.297 1.00 2.44 C C
ATOM 8974 NHl ARG 1 282 9.914 -13.339 9.690 1.00 2.04 C N
ATOM 8975 NH2 ARG 1 282 12.099 -13.847 10.167 1.00 3.44 C N
ATOM 8976 C ARG 1 282 8.144 -13.952 2.898 1.00 5.32 C C
ATOM 8977 O ARG 1 282 6.924 -13.854 3.022 1.00 5.95 C O
ATOM 8978 N GLN 1 283 8.794 -13.551 1.812 1.00 5.50 C N
ATOM 8979 CA GLN 1 283 8.083 -12.995 0.671 1.00 5.80 C C
ATOM 8980 CB GLN 1 283 9.064 -12.580 -0.421 1.00 6.19 C C
ATOM 8981 CG GLN 1 283 9.908 -11.381 -0.047 1.00 9.68 C C
ATOM 8982 CD GLN 1 283 11.088 -11.192 -0.971 1.00 13.92 C C
ATOM 8983 OE1 GLN I 283 11.266 -11.939 -1.934 1.00 16.20 C O
ATOM 8984 NE2 GLN I 283 11.885 -10.164 -0.706 1.00 14.17 C N
ATOM 8985 C GLN 1 283 7.071 -13.988 0.120 1.00 5.44 C C ATOM 8986 O GLN I 283 6.069 -13.598 -0.479 1.00 5.43 C o
ATOM 8987 N GLN I 284 7.302 -15.269 0.387 1.00 5.26 c N
ATOM 8988 CA GLN I 284 6.465 -16.321 -0.172 1.00 5.18 c c
ATOM 8989 CB GLN I 284 7.303 -17.549 -0.517 1.00 5.32 c c
ATOM 8990 CG GLN I 284 7.689 -17.619 -1.981 1.00 6.85 c c
ATOM 8991 CD GLN I 284 8.548 -18.821 -2.304 1.00 9.21 c c
ATOM 8992 OE1 GLN I 284 9.398 -19.227 -1.511 1.00 9.74 c o
ATOM 8993 NE2 GLN I 284 8.332 -19.400 -3.477 1.00 9.79 c N
ATOM 8994 C GLN I 284 5.345 -16.705 0.779 1.00 4.67 c c
ATOM 8995 O GLN I 284 4.485 -17.520 0.447 1.00 4.19 c o
ATOM 8996 N SE I 285 5.367 -16.116 1.968 1.00 4.51 c N
ATOM 8997 CA SE I 285 4.457 -16.516 3.027 1.00 4.39 c c
ATOM 8998 CB SE I 285 5.218 -16.729 4.336 1.00 4.13 c c
ATOM 8999 OG SE I 285 6.328 -17.588 4.146 1.00 4.40 c o
ATOM 9000 C SER I 285 3.359 -15.481 3.220 1.00 4.44 c c
ATOM 9001 O SER I 285 3.483 -14.335 2.785 1.00 4.82 c o
ATOM 9002 N TYR I 286 2.268 -15.908 3.842 1.00 4.53 c N
ATOM 9003 CA TYR I 286 1.194 -15.002 4.213 1.00 4.80 c c
ATOM 9004 CB TYR I 286 -0.116 -15.441 3.559 1.00 4.88 c c
ATOM 9005 CG TYR I 286 -0.135 -15.272 2.059 1.00 5.68 c c
ATOM 9006 CD1 TYR I 286 0.713 -16.013 1.245 1.00 7.34 c c
ATOM 9007 CE1 TYR I 286 0.695 -15.864 -0.126 1.00 9.02 c c
ATOM 9008 CZ TYR I 286 -0.190 -14.979 -0.701 1.00 9.40 c c
ATOM 9009 OH TYR I 286 -0.206 -14.824 -2.066 1.00 10.44 c : o
ATOM 9010 CE2 TYR I 286 -1.054 -14.244 0.083 1.00 9.38 c c
ATOM 9011 CD2 TYR I 286 -1.024 -14.395 1.453 1.00 7.39 c c
ATOM 9012 C TYR I 286 1.037 -14.978 5.726 1.00 4.76 C c
ATOM 9013 O TYR I 286 1.499 -15.883 6.421 1.00 5.25 c o
ATOM 9014 N SER I 287 0.403 -13.929 6.234 1.00 4.52 c N
ATOM 9015 CA SER I 287 -0.072 -13.924 7.609 1.00 4.45 c c
ATOM 9016 CB SER I 287 0.779 -12.989 8.470 1.00 4.57 c c
ATOM 9017 OG SER I 287 0.113 -12.662 9.678 1.00 4.38 c o
ATOM 9018 C SER I 287 -1.535 -13.516 7.675 1.00 4.61 c c
ATOM 9019 O SER I 287 -1.920 -12.460 7.172 1.00 4.40 c o
ATOM 9020 N ILE I 288 -2.364 -14.425 8.171 1.00 5.11 c N
ATOM 9021 CA ILE I 288 -3.788 -14.171 8.302 1.00 5.81 c c
ATOM 9022 CB ILE I 288 -4.610 -15.393 7.863 1.00 5.52 c c
ATOM 9023 CGI ILE I 288 -3.811 -16.253 6.878 1.00 5.47 c c
ATOM 9024 CD1 ILE I 288 -3.975 -15.852 5.429 1.00 6.23 c c
ATOM 9025 CG2 ILE I 288 -5.939 -14.957 7.271 1.00 6.22 c c
ATOM 9026 C ILE I 288 -4.123 -13.848 1 9.750 1.00 6.71 c c
ATOM 9027 O ILE I 288 -3.759 -14.593 10.660 1.00 7.30 c o
ATOM 9028 N MET I 289 -4.874 -12.771 9.952 1.00 7.71 c N
ATOM 9029 CA MET I 289 -5.451 -12.476 11.257 1.00 8.57 C C
ATOM 9030 CB MET I 289 -6.099 -11.090 11.246 1.00 8.71 C C
ATOM 9031 CG MET I 289 -6.131 -10.412 12.603 1.00 9.70 C C
ATOM 9032 SD MET I 289 -7.100 -8.895 12.581 1.00 12.59 C S
ATOM 9033 CE MET I 289 -8.569 -9.452 11.721 1.00 12.41 C C
ATOM 9034 C MET I 289 -6.477 -13.538 11.658 1.00 9.12 C C
ATOM 9035 O MET I 289 -7.322 -13.925 10.851 1.00 9.31 C O
ATOM 9036 N SER I 290 -6.406 -13.998 12.907 1.00 9.80 C N
ATOM 9037 CA SER I 290 -7.290 -15.062 13.388 1.00 10.49 C C
ATOM 9038 CB SER I 290 -6.494 -16.195 14.035 1.00 10.64 C C
ATOM 9039 OG SER I 290 -7.316 -17.328 14.257 1.00 11.99 C O
ATOM 9040 C SER 1 290 -8.385 -14.573 14.335 1.00 10.75 C C
ATOM 9041 O SER 1 290 -9.563 -14.595 13.980 1.00 10.89 C O
ATOM 9042 N ILE I 291 8.018 -14.243 15.571 1.00 11.04 C N
ATOM 9043 CA ILE I 291 -8.955 -13.562 16.461 1.00 11.41 C C
ATOM 9044 CB ILE I 291 -9.796 -14.539 17.305 1.00 11.80 C C
ATOM 9045 CGI ILE I 291 -9.096 -15.893 17.419 1.00 11.81 C C ATOM 9046 CD1 ILE I 291 -8.227 -16.028 18.647 1.00 11.76 C c
ATOM 9047 CG2 ILE I 291 -11.179 -14.707 16.700 1.00 12.39 c c
ATOM 9048 C ILE I 291 -8.349 -12.481 17.346 1.00 11.13 C c
ATOM 9049 O ILE I 291 -7.316 -12.681 17.986 1.00 10.55 c o
ATOM 9050 N ILE I 292 -9.034 -11.343 17.398 1.00 11.36 c N
ATOM 9051 CA ILE I 292 -8.605 -10.215 18.211 1.00 11.82 c c
ATOM 9052 CB ILE I 292 -8.651 -8.884 17.421 1.00 11.86 c c
ATOM 9053 CGI ILE I 292 -9.052 -9.127 15.963 1.00 13.42 c c
ATOM 9054 CD1 ILE I 292 -7.968 -9.771 15.126 1.00 15.86 c c
ATOM 9055 CG2 ILE I 292 -7.311 -8.160 17.508 1.00 10.85 c c
ATOM 9056 C ILE I 292 -9.486 -10.092 19.444 1.00 11.72 C c
ATOM 9057 O ILE I 292 -10.713 -10.029 19.346 1.00 11.28 c o
ATOM 9058 N LYS I 293 -8.857 -10.180 20.607 1.00 12.11 c N
ATOM 9059 CA LYS I 293 -9.479 -9.728 21.834 1.00 12.92 c c
ATOM 9060 CB LYS I 293 -9.599 -10.889 22.820 1.00 13.15 c c
ATOM 9061 CG LYS I 293 -10.034 -12.194 22.174 1.00 14.17 c c
ATOM 9062 CD LYS I 293 -10.958 -12.974 23.091 1.00 15.37 c c
ATOM 9063 CE LYS I 293 -11.869 -13.899 22.305 1.00 16.68 c c
ATOM 9064 NZ LYS I 293 -12.822 -14.614 23.197 1.00 18.18 c N
ATOM 9065 C LYS I 293 -8.670 -8.584 22.433 1.00 13.32 c c
ATOM 9066 O LYS I 293 -7.518 -8.366 22.055 1.00 13.17 c o
ATOM 9067 N GLU I 294 -9.337 -7.759 23.233 1.00 14.07 c N
ATOM 9068 CA GLU I 294 -8.714 -6.572 23.805 1.00 15.07 c c
ATOM 9069 CB GLU I 294 -9.608 -5.975 24.896 1.00 15.94 c c
ATOM 9070 CG GLU I 294 -10.872 -5.307 24.373 1.00 19.87 c c
ATOM 9071 CD GLU I 294 -11.569 -4.471 25.427 1.00 23.88 c c
ATOM 9072 OE1 GLU I 294 -10.994 -3.449 25.854 1.00 23.75 c : o
ATOM 9073 OE2 GLU I 294 -12.723 -4.799 25.777 1.00 25.81 c : o
ATOM 9074 C GLU I 294 -7.324 -6.878 24.362 1.00 14.40 c c
ATOM 9075 O GLU I 294 -6.433 -6.031 24.319 1.00 14.33 c o
ATOM 9076 N GLU I 295 -7.144 -8.092 24.879 1.00 13.97 c N
ATOM 9077 CA GLU I 295 -5.908 -8.452 25.568 1.00 13.84 c c
ATOM 9078 CB GLU I 295 -6.161 -8.721 27.055 1.00 14.67 c c
ATOM 9079 CG GLU I 295 -7.620 -8.914 27.427 1.00 17.56 c c
ATOM 9080 CD GLU I 295 -8.245 -10.112 26.743 1.00 21.41 c c
ATOM 9081 OE1 GLU I 295 -8.990 -9.909 25.761 1.00 22.35 c o
ATOM 9082 OE2 GLU I 295 -8.090 -11.241 27.257 1.00 23.20 c : o
ATOM 9083 C GLU I 295 -5.166 -9.630 24.933 1.00 12.77 c c
ATOM 9084 O GLU I 295 -4.166 -10.100 25.476 1.00 12.58 c o
ATOM 9085 N VAL I 296 -5.701 -10.162 23.838 1.00 11.72 c N
ATOM 9086 CA VAL I 296 -4.970 -11.150 23.051 1.00 10.65 c c
ATOM 9087 CB VAL I 296 -5.245 -12.589 23.517 1.00 10.47 c c
ATOM 9088 CGI VAL I 296 -4.277 -13.546 22.846 1.00 9.77 c c
ATOM 9089 CG2 VAL I 296 -5.118 -12.688 25.026 1.00 11.31 c c
ATOM 9090 C VAL I 296 -5.245 -11.039 21.562 1.00 10.26 c c
ATOM 9091 O VAL I 296 -6.395 -10.940 21.133 1.00 10.09 c o
ATOM 9092 N LEU I 297 -4.184 -11.178 20.777 1.00 9.77 c N
ATOM 9093 CA LEU I 297 -4.302 -11.269 19.332 1.00 8.97 c c
ATOM 9094 CB LEU I 297 -3.577 -10.097 18.672 1.00 8.64 c c
ATOM 9095 CG LEU I 297 -3.382 -10.209 17.160 1.00 9.01 c c
ATOM 9096 CD1 LEU I 297 -4.721 -10.384 16.459 1.00 9.79 c c
ATOM 9097 CD2 LEU I 297 -2.645 -8.994 16.620 1.00 9.43 c c
ATOM 9098 C LEU I 297 -3.725 -12.587 18.829 1.00 8.34 c c
ATOM 9099 O LEU I 297 -2.565 -12.908 19.089 1.00 8.64 c o
ATOM 9100 N ALA I 298 -4.545 -13.352 18.116 1.00 7.21 c N
ATOM 9101 CA ALA I 298 -4.095 -14.600 17.515 1.00 6.33 c c
ATOM 9102 CB ALA I 298 -4.908 -15.770 18.047 1.00 6.68 c c
ATOM 9103 C ALA I 298 -4.207 -14.524 16.002 1.00 5.85 c c
ATOM 9104 O ALA I 298 -5.179 -13.991 15.468 1.00 5.96 c o
ATOM 9105 N TY I 299 -3.197 -15.040 15.314 1.00 5.28 c N ATOM 9106 CA TY I 299 -3.197 -15.042 13.861 1.00 4.63 C c
ATOM 9107 CB TY I 299 -2.583 -13.749 13.324 1.00 4.36 c c
ATOM 9108 CG TY I 299 -1.177 -13.490 13.812 1.00 4.34 c c
ATOM 9109 CD1 TY I 299 -0.080 -13.970 13.110 1.00 4.48 c : c
ATOM 9110 CE1 TYR I 299 1.207 -13.733 13.549 1.00 4.55 c c
ATOM 9111 CZ TYR I 299 1.409 -13.011 14.705 1.00 3.72 c c
ATOM 9112 OH TYR I 299 2.690 -12.775 15.149 1.00 2.38 c o
ATOM 9113 CE2 TYR I 299 0.336 -12.526 15.422 1.00 4.13 c c
ATOM 9114 CD2 TYR I 299 -0.947 -12.767 14.975 1.00 4.38 c : c
ATOM 9115 C TYR I 299 -2.440 -16.243 13.322 1.00 4.32 c c
ATOM 9116 O TYR I 299 -1.602 -16.822 14.012 1.00 4.67 c o
ATOM 9117 N VAL I 300 -2.746 -16.622 12.087 1.00 3.87 c N
ATOM 9118 CA VAL I 300 -2.130 -17.792 11.486 1.00 3.57 c c
ATOM 9119 CB VAL I 300 -3.169 -18.702 10.805 1.00 3.52 c c
ATOM 9120 CGI VAL I 300 -2.475 -19.749 9.943 1.00 3.44 c c
ATOM 9121 CG2 VAL I 300 -4.053 -19.368 11.851 1.00 3.90 c : c
ATOM 9122 C VAL I 300 -1.060 -17.392 10.482 1.00 3.53 c c
ATOM 9123 O VAL I 300 -1.299 -16.575 9.593 1.00 3.68 c o
ATOM 9124 N VAL I 301 0.148 -17.899 10.695 1.00 3.41 c N
ATOM 9125 CA VAL I 301 1.193 -17.816 9.689 1.00 3.36 c c
ATOM 9126 CB VAL I 301 2.593 -17.825 10.324 1.00 3.24 c c
ATOM 9127 CGI VAL I 301 3.655 -18.061 9.261 1.00 3.76 c c
ATOM 9128 CG2 VAL I 301 2.849 -16.519 11.059 1.00 3.10 c c
ATOM 9129 C VAL I 301 1.084 -18.962 8.695 1.00 3.48 c c
ATOM 9130 O VAL I 301 0.647 -20.061 9.037 1.00 3.92 c o
ATOM 9131 N GLN I 302 1.466 -18.684 7.456 1.00 3.21 c N
ATOM 9132 CA GLN I 302 1.274 -19.625 6.368 1.00 3.01 c c
ATOM 9133 CB GLN I 302 0.090 -19.202 5.504 1.00 3.24 c c
ATOM 9134 CG GLN I 302 -0.067 -20.021 4.239 1.00 5.21 c c
ATOM 9135 CD GLN I 302 -1.479 -19.984 3.701 1.00 7.54 c c
ATOM 9136 OE1 GLN I 302 -2.435 -19.784 4.449 1.00 7.28 c o
ATOM 9137 NE2 GLN I 302 -1.616 -20.143 2.390 1.00 9.27 c N
ATOM 9138 C GLN I 302 2.533 -19.693 5.523 1.00 2.42 c c
ATOM 9139 O GLN I 302 2.881 -18.736 4.832 1.00 2.40 c o
ATOM 9140 N LEU I 303 3.292 -20.765 5.707 1.00 2.00 c N
ATOM 9141 CA LEU I 303 4.607 -20.868 5.104 1.00 2.00 c c
ATOM 9142 CB LEU I 303 5.628 -21.358 6.130 1.00 2.00 c c
ATOM 9143 CG LEU I 303 5.663 -20.559 7.434 1.00 2.00 c c
ATOM 9144 CD1 LEU I 303 6.712 -21.118 8.382 1.00 2.00 c c
ATOM 9145 CD2 LEU I 303 5.918 -19.085 7.154 1.00 2.00 c c
ATOM 9146 C LEU I 303 4.564 -21.805 3.909 1.00 2.00 c c
ATOM 9147 O LEU I 303 3.658 -22.630 3.794 1.00 2.45 c o
ATOM 9148 N PRO I 304 5.499 -21.620 2.970 1.00 2.00 c N
ATOM 9149 CA PRO I 304 5.617 -22.519 1.840 1.00 2.07 c c
ATOM 9150 CB PRO I 304 6.326 -21.656 0.803 1.00 2.00 c c
ATOM 9151 CG PRO I 304 7.221 -20.775 1.620 1.00 2.00 c c
ATOM 9152 CD PRO I 304 6.564 -20.601 2.973 1.00 2.06 c c
ATOM 9153 C PRO I 304 6.492 -23.711 2.194 1.00 2.11 c c
ATOM 9154 O PRO I 304 7.544 -23.530 2.809 1.00 2.13 c o
ATOM 9155 N ALA I 305 5.903 -24.902 2.097 1.00 30.00 c N
ATOM 9156 CA ALA I 305 6.371 -25.959 1.180 1.00 30.00 c c
ATOM 9157 CB ALA I 305 5.841 -27.314 1.627 1.00 30.00 c c
ATOM 9158 C ALA I 305 6.011 -25.690 -0.310 1.00 30.00 c c
ATOM 9159 O ALA I 305 5.614 -24.571 -0.624 1.00 30.00 c o
ATOM 9160 N TYR I 306 5.840 -26.756 -1.125 1.00 13.49 c N
ATOM 9161 CA TYR I 306 6.433 -26.943 -2.522 1.00 13.70 c c
ATOM 9162 CB TYR I 306 7.412 -28.117 -2.435 1.00 13.93 c c
ATOM 9163 CG TYR I 306 8.486 -28.217 -3.491 1.00 14.08 c c
ATOM 9164 CD1 TYR I 306 8.717 -29.447 -4.102 1.00 14.59 c : c
ATOM 9165 CE1 TYR I 306 9.982 -29.819 -4.531 1.00 14.82 c c ATOM 9166 CZ TY I 306 11.002 -28.893 -4.523 1.00 14.52 C c
ATOM 9167 OH TYR I 306 12.189 -29.164 -5.167 1.00 13.02 c o
ATOM 9168 CE2 TYR I 306 10.781 -27.632 -4.011 1.00 15.22 c c
ATOM 9169 CD2 TYR I 306 9.534 -27.303 -3.495 1.00 14.61 c c
ATOM 9170 C TYR I 306 5.391 -27.297 -3.661 1.00 13.68 c c
ATOM 9171 O TYR I 306 4.296 -27.738 -3.325 1.00 13.95 c o
ATOM 9172 N GLY I 307 5.786 -27.316 -4.962 1.00 13.54 c N
ATOM 9173 CA GLY I 307 5.057 -28.108 -6.046 1.00 13.37 c c
ATOM 9174 C GLY I 307 5.290 -27.995 -7.585 1.00 13.47 c c
ATOM 9175 O GLY I 307 5.871 -27.017 -8.054 1.00 13.90 c o
ATOM 9176 N VAL I 308 4.808 -28.976 -8.370 1.00 13.31 c N
ATOM 9177 CA VAL I 308 3.931 -28.717 -9.548 1.00 13.30 c c
ATOM 9178 CB VAL I 308 3.187 -27.383 -9.404 1.00 13.03 c c
ATOM 9179 CGI VAL I 308 1.935 -27.380 -10.261 1.00 13.62 c c
ATOM 9180 CG2 VAL I 308 2.849 -27.116 -7.951 1.00 12.86 c c
ATOM 9181 C VAL I 308 4.596 -28.668 -10.927 1.00 13.58 c c
ATOM 9182 O VAL I 308 5.407 -29.530 -11.271 1.00 13.71 c o
ATOM 9183 N ILE I 309 4.541 -27.470 -11.498 1.00 4.08 C N
ATOM 9184 CA ILE I 309 5.611 -26.532 -11.251 1.00 4.84 c c
ATOM 9185 CB ILE I 309 6.204 -26.810 -9.854 1.00 4.89 c c
ATOM 9186 CGI ILE I 309 5.086 -26.815 -8.801 1.00 5.85 c c
ATOM 9187 CD1 ILE I 309 4.233 -25.561 -8.803 1.00 8.12 c c
ATOM 9188 CG2 ILE I 309 7.308 -25.817 -9.517 1.00 4.44 c c
ATOM 9189 C ILE I 309 6.637 -26.814 -12.345 1.00 5.23 c c
ATOM 9190 O ILE I 309 6.299 -27.437 -13.352 1.00 5.92 c o
ATOM 9191 N ASP I 310 7.864 -26.330 -12.187 1.00 5.33 c N
ATOM 9192 CA ASP I 310 9.004 -26.924 -12.889 1.00 5.83 c c
ATOM 9193 CB ASP I 310 9.086 -28.423 -12.589 1.00 6.21 c c
ATOM 9194 CG ASP I 310 9.193 -28.716 -11.104 1.00 7.19 c c
ATOM 9195 OD1 ASP I 310 8.350 -29.478 -10.583 1.00 7.74 c o
ATOM 9196 OD2 ASP I 310 10.151 -28.228 -10.467 1.00 7.58 c o
ATOM 9197 C ASP I 310 8.997 -26.705 -14.408 1.00 6.02 c c
ATOM 9198 O ASP I 310 9.656 -27.438 -15.146 1.00 6.05 c o
ATOM 9199 N THR I 311 8.273 -25.687 -14.866 1.00 6.24 c N
ATOM 9200 CA THR I 311 8.429 -25.173 -16.229 1.00 6.14 c c
ATOM 9201 CB THR I 311 7.231 -24.299 -16.630 1.00 5.69 c c
ATOM 9202 OG1 THR I 311 6.093 -24.646 -15.830 1.00 5.34 c o
ATOM 9203 CG2 THR I 311 6.897 -24.500 -18.092 1.00 7.10 c c
ATOM 9204 C THR I 311 9.682 -24.313 -16.335 1.00 6.78 c c
ATOM 9205 O THR I 311 9.970 -23.530 -15.430 1.00 7.33 c o
ATOM 9206 N PRO I 312 10.330 -24.318 -17.509 1.00 7.00 c N
ATOM 9207 CA PRO I 312 11.470 -23.419 -17.668 1.00 7.23 c c
ATOM 9208 CB PRO I 312 12.060 -23.834 -19.020 1.00 7.00 c c
ATOM 9209 CG PRO I 312 10.936 -24.505 -19.747 1.00 6.59 c c
ATOM 9210 CD PRO I 312 10.098 -25.159 -18.697 1.00 6.99 c c
ATOM 9211 C PRO I 312 11.016 -21.962 -17.703 1.00 7.69 c c
ATOM 9212 O PRO I 312 9.943 -21.670 -18.228 1.00 7.55 c o
ATOM 9213 N CYS I 313 11.755 -21.077 -17.041 1.00 8.10 c N
ATOM 9214 CA CYS I 313 11.668 -19.654 -17.353 1.00 8.54 c c
ATOM 9215 CB CYS I 313 11.082 -18.852 -16.186 1.00 8.77 c c
ATOM 9216 SG CYS I 313 10.025 -19.785 -15.057 1.00 10.74 c s
ATOM 9217 C CYS I 313 13.000 -19.058 -17.780 1.00 8.19 c c
ATOM 9218 O CYS I 313 14.035 -19.725 -17.760 1.00 8.07 c o
ATOM 9219 N TRP I 314 12.964 -17.777 -18.126 1.00 7.93 c N
ATOM 9220 CA TRP I 314 14.162 -17.035 -18.473 1.00 7.80 c c
ATOM 9221 CB TRP I 314 14.563 -17.322 -19.919 1.00 8.13 c c
ATOM 9222 CG TRP I 314 13.457 -17.091 -20.902 1.00 9.09 c c
ATOM 9223 CD1 TRP I 314 13.295 -16.003 -21.710 1.00 10.26 c c
ATOM 9224 NE1 TRP I 314 12.219 -16.189 -22.546 1.00 10.86 c : N
ATOM 9225 CE2 TRP I 314 11.671 -17.421 -22.298 1.00 10.68 c c ATOM 9226 CD2 T P I 314 12.426 -18.020 -21.269 1.00 10.49 C C
ATOM 9227 CE3 TRP I 314 12.083 -19.308 -20.842 1.00 11.67 C C
ATOM 9228 CZ3 TRP I 314 11.009 -19.946 -21.447 1.00 12.98 C C
ATOM 9229 CH2 TRP I 314 10.268 -19.318 -22.457 1.00 12.74 C C
ATOM 9230 CZ2 TRP I 314 10.580 -18.059 -22.895 1.00 11.73 C C
ATOM 9231 C TRP I 314 13.899 -15.550 -18.298 1.00 7.34 C C
ATOM 9232 O TRP I 314 12.764 -15.091 -18.427 1.00 7.47 C O
ATOM 9233 N LYS I 315 14.936 -14.815 -17.920 1.00 6.75 C N
ATOM 9234 CA LYS I 315 14.833 -13.372 -17.823 1.00 6.37 C C
ATOM 9235 CB LYS I 315 15.493 -12.875 -16.541 1.00 6.38 C C
ATOM 9236 CG LYS I 315 14.992 -11.522 -16.065 1.00 6.55 C C
ATOM 9237 CD LYS I 315 15.692 -11.117 -14.778 1.00 8.01 C C
ATOM 9238 CE LYS I 315 15.198 -9.776 -14.269 1.00 8.78 C C
ATOM 9239 NZ LYS I 315 16.141 -9.189 -13.276 1.00 10.21 C N
ATOM 9240 C LYS I 315 15.468 -12.711 -19.036 1.00 6.32 C C
ATOM 9241 O LYS 1 315 16.510 -13.153 -19.523 1.00 6.21 C O
ATOM 9242 N LEU 1 316 14.766 -11.724 -19.584 1.00 6.58 C N
ATOM 9243 C A LEU I 316 15.231 -10.992 -20.758 1.00 7.02 C C
ATOM 9244 CB LEU I 316 14.122 -10.908 -21.809 1.00 6.64 C C
ATOM 9245 CG LEU I 316 14.308 -9.874 -22.922 1.00 6.21 C C
ATOM 9246 CD1 LEU I 316 15.563 -10.150 -23.731 1.00 5.94 C C
ATOM 9247 CD2 LEU I 316 13.082 -9.824 -23.819 1.00 6.57 C C
ATOM 9248 C LEU 1 316 15.675 -9.588 -20.372 1.00 7.77 C C
ATOM 9249 O LEU 1 316 14.865 -8.768 -19.941 1.00 8.47 C O
ATOM 9250 N HIS I 317 16.956 -9.302 -20.563 1.00 8.05 C N
ATOM 9251 CA HIS I 317 17.422 -7.929 -20.547 1.00 8.21 C C
ATOM 9252 CB HIS I 317 18.641 -7.786 -19.640 1.00 9.04 C C
ATOM 9253 CG HIS I 317 18.644 -8.734 -18.483 1.00 11.41 C C
ATOM 9254 ND1 HIS I 317 18.314 -8.347 -17.202 1.00 13.62 C N
ATOM 9255 CE1 HIS I 317 18.423 -9.383 -16.389 1.00 14.91 C C
ATOM 9256 NE2 HIS I 317 18.811 -10.428 -17.097 1.00 14.25 C N
ATOM 9257 CD2 HIS I 317 18.960 -10.048 -18.409 1.00 12.67 C C
ATOM 9258 C HIS 1 317 17.760 -7.469 -21.950 1.00 7.39 C C
ATOM 9259 O HIS 1 317 17.881 -8.278 -22.869 1.00 7.23 C O
ATOM 9260 N THR I 318 17.997 -6.172 -22.086 1.00 7.11 C N
ATOM 9261 CA THR I 318 17.745 -5.476 -23.333 1.00 6.56 C C
ATOM 9262 CB THR I 318 16.268 -5.093 -23.468 1.00 6.28 C C
ATOM 9263 OG1 THR I 318 15.652 -5.909 -24.471 1.00 6.33 C O
ATOM 9264 CG2 THR I 318 16.141 -3.634 -23.866 1.00 6.52 C C
ATOM 9265 C THR I 318 18.563 -4.201 -23.357 1.00 6.58 C C
ATOM 9266 O THR I 318 18.437 -3.356 -22.472 1.00 6.67 C O
ATOM 9267 N SER I 319 19.378 -4.044 -24.390 1.00 6.81 C N
ATOM 9268 CA SER I 319 20.173 -2.837 -24.533 1.00 7.31 C C
ATOM 9269 CB SER I 319 21.633 -3.105 -24.159 1.00 7.14 C C
ATOM 9270 OG SER I 319 22.309 -1.904 -23.825 1.00 6.84 C O
ATOM 9271 C SER I 319 20.069 -2.273 -25.945 1.00 7.93 C C
ATOM 9272 O SER I 319 19.736 -2.996 -26.887 1.00 8.65 C O
ATOM 9273 N PRO 1 320 20.242 -0.952 -26.075 1.00 8.08 C N
ATOM 9274 CA PRO I 320 20.052 -0.299 -27.363 1.00 8.34 C C
ATOM 9275 CB PRO 1 320 20.263 1.187 -27.047 1.00 7.99 C C
ATOM 9276 CG PRO 1 320 20.887 1.228 -25.680 1.00 8.01 C C
ATOM 9277 CD PRO 1 320 20.384 0.015 -24.977 1.00 8.10 C C
ATOM 9278 C PRO 1 320 21.061 -0.770 -28.400 1.00 9.03 C C
ATOM 9279 O PRO 1 320 22.135 -1.262 -28.053 1.00 8.74 C O
ATOM 9280 N LEU 1 321 20.711 -0.594 -29.669 1.00 10.31 C N
ATOM 9281 CA LEU I 321 21.427 -1.228 -30.766 1.00 11.63 C C
ATOM 9282 CB LEU I 321 20.792 -2.576 -31.105 1.00 11.31 C C
ATOM 9283 CG LEU I 321 21.681 -3.600 -31.812 1.00 10.97 C C
ATOM 9284 CD 1 LEU I 321 20.835 -4.621 -32.549 1.00 10.04 C C
ATOM 9285 CD2 LEU I 321 22.652 -2.914 -32.761 1.00 10.69 C C ATOM 9286 C LEU 1 321 21.412 -0.317 -31.989 1.00 12.92 C C
ATOM 9287 O LEU 1 321 20.351 0.114 -32.441 1.00 13.29 C O
ATOM 9288 N CYS 1 322 22.601 0.013 -32.486 1.00 13.39 C N
ATOM 9289 CA CYS 1 322 22.751 0.987 -33.563 1.00 14.16 C C
ATOM 9290 CB CYS 1 322 23.359 2.288 -33.036 1.00 13.72 C C
ATOM 9291 SG CYS 1 322 22.632 2.898 -31.504 1.00 13.42 C S
ATOM 9292 C CYS 1 322 23.622 0.441 -34.690 1.00 15.46 C C
ATOM 9293 O CYS 1 322 24.646 -0.196 -34.446 1.00 15.94 C O
ATOM 9294 N TH 1 323 23.265 0.802 -35.919 1.00 16.70 C N
ATOM 9295 CA THR 1 323 24.152 0.675 -37.075 1.00 17.84 C C
ATOM 9296 CB THR 1 323 23.429 1.117 -38.359 1.00 17.50 C C
ATOM 9297 OG1 THR 1 323 22.416 2.076 -38.031 1.00 15.70 C O
ATOM 9298 CG2 THR I 323 22.786 -0.076 -39.047 1.00 18.05 C C
ATOM 9299 C THR 1 323 25.403 1.536 -36.918 1.00 19.54 C C
ATOM 9300 O THR 1 323 25.408 2.477 -36.124 1.00 19.84 C O
ATOM 9301 N THR 1 324 26.352 1.379 -37.840 1.00 21.17 C N
ATOM 9302 CA THR 1 324 27.430 2.358 -37.967 1.00 22.89 C C
ATOM 9303 CB THR 1 324 28.687 1.950 -37.188 1.00 22.69 C C
ATOM 9304 OG1 THR 1 324 28.403 0.800 -36.381 1.00 22.10 C O
ATOM 9305 CG2 THR I 324 29.150 3.094 -36.300 1.00 22.03 C C
ATOM 9306 C THR 1 324 27.815 2.806 -39.378 1.00 24.39 C C
ATOM 9307 O THR 1 324 28.495 3.820 -39.537 1.00 24.53 C O
ATOM 9308 N ASN 1 325 27.330 2.106 -40.398 1.00 25.72 C N
ATOM 9309 CA ASN 1 325 27.321 2.661 -41.751 1.00 27.01 C C
ATOM 9310 CB ASN 1 325 28.628 2.344 -42.484 1.00 27.37 C C
ATOM 9311 CG ASN 1 325 29.720 3.360 -42.199 1.00 28.46 C C
ATOM 9312 OD1 ASN I 325 29.982 4.252 -43.007 1.00 30.37 C O
ATOM 9313 ND2 ASN I 325 30.364 3.229 -41.045 1.00 28.78 C N
ATOM 9314 C ASN 1 325 26.125 2.199 -42.576 1.00 27.36 C C
ATOM 9315 O ASN 1 325 25.455 1.228 -42.226 1.00 27.94 C O
ATOM 9316 N SER I 330 24.776 3.883 -38.461 1.00 35.76 C N
ATOM 9317 CA SER 1 330 24.479 5.303 -38.606 1.00 35.01 C C
ATOM 9318 CB SER 1 330 24.922 5.803 -39.983 1.00 35.47 C C
ATOM 9319 OG SER 1 330 24.296 5.067 -41.019 1.00 33.31 C O
ATOM 9320 C SER 1 330 22.992 5.574 -38.405 1.00 34.35 C C
ATOM 9321 O SER 1 330 22.148 4.769 -38.798 1.00 34.33 C O
ATOM 9322 N ASN 1 331 22.677 6.688 -37.752 1.00 32.48 C N
ATOM 9323 CA ASN 1 331 21.365 7.314 -37.886 1.00 30.72 C C
ATOM 9324 CB ASN 1 331 21.065 7.642 -39.357 1.00 31.31 C C
ATOM 9325 CG ASN I 331 21.961 8.740 -39.916 1.00 32.11 C C
ATOM 9326 OD1 ASN 1 331 22.615 9.469 -39.170 1.00 32.54 C O
ATOM 9327 ND2 ASN I 331 21.941 8.901 -41.235 1.00 31.30 C N
ATOM 9328 C ASN 1 331 20.188 6.532 -37.282 1.00 28.71 C C
ATOM 9329 O ASN 1 331 19.038 6.940 -37.444 1.00 29.07 C O
ATOM 9330 N ILE 1 332 20.450 5.399 -36.629 1.00 25.44 C N
ATOM 9331 CA ILE 1 332 19.354 4.517 -36.200 1.00 21.83 C C
ATOM 9332 CB ILE 1 332 18.777 3.711 -37.387 1.00 21.42 C C
ATOM 9333 CGI ILE 1 332 17.534 2.929 -36.961 1.00 19.89 C C
ATOM 9334 CD1 ILE 1 332 16.273 3.385 -37.652 1.00 17.67 C C
ATOM 9335 CG2 ILE 1 332 19.828 2.777 -37.965 1.00 20.61 C C
ATOM 9336 C ILE 1 332 19.679 3.570 -35.035 1.00 20.37 C C
ATOM 9337 O ILE 1 332 20.593 2.751 -35.134 1.00 19.95 C O
ATOM 9338 N CYS 1 333 18.816 3.561 -34.019 1.00 18.27 C N
ATOM 9339 CA CYS 1 333 18.930 2.597 -32.921 1.00 16.47 C C
ATOM 9340 CB CYS 1 333 19.646 3.216 -31.720 1.00 16.14 C C
ATOM 9341 SG CYS 1 333 21.144 4.124 -32.136 1.00 17.09 C S
ATOM 9342 C CYS 1 333 17.615 1.958 -32.475 1.00 15.73 C C
ATOM 9343 O CYS 1 333 16.556 2.586 -32.511 1.00 15.43 C O
ATOM 9344 N LEU 1 334 17.761 0.811 -31.819 1.00 15.06 C N
ATOM 9345 CA LEU I 334 16.643 -0.021 -31.394 1.00 13.79 C C ATOM 9346 CB LEU I 334 16.607 -1.319 -32.203 1.00 13.39 C C
ATOM 9347 CG LEU I 334 16.482 -1.230 -33.725 1.00 13.93 C C
ATOM 9348 CD1 LEU I 334 15.861 -2.496 -34.287 1.00 14.20 C C
ATOM 9349 CD2 LEU I 334 15.686 -0.009 -34.151 1.00 14.52 C C
ATOM 9350 C LEU 1 334 16.852 -0.366 -29.928 1.00 13.22 C C
ATOM 9351 O LEU 1 334 17.968 -0.685 -29.520 1.00 13.31 C O
ATOM 9352 N TH 1 335 15.768 -0.423 -29.167 1.00 12.58 C N
ATOM 9353 CA THR I 335 15.790 -1.126 -27.892 1.00 12.17 C C
ATOM 9354 CB THR 1 335 15.955 -0.158 -26.706 1.00 12.02 C C
ATOM 9355 OG1 THR I 335 16.652 1.018 -27.139 1.00 12.64 C O
ATOM 9356 CG2 THR I 335 16.739 -0.825 -25.582 1.00 11.47 C C
ATOM 9357 C THR 1 335 14.523 -1.942 -27.703 1.00 11.97 C C
ATOM 9358 O THR 1 335 13.423 -1.471 -27.990 1.00 11.93 C O
ATOM 9359 N ARG I 336 14.700 -3.216 -27.379 1.00 11.60 C N
ATOM 9360 CA ARG I 336 13.573 -4.131 -27.260 1.00 12.15 C C
ATOM 9361 CB ARG I 336 14.066 -5.579 -27.235 1.00 12.16 C C
ATOM 9362 CG ARG I 336 13.124 -6.566 -27.906 1.00 12.67 C C
ATOM 9363 CD ARG I 336 13.876 -7.491 -28.846 1.00 12.52 C C
ATOM 9364 NE ARG I 336 14.414 -8.649 -28.144 1.00 12.35 C N
ATOM 9365 CZ ARG 1 336 13.675 -9.665 -27.713 1.00 12.54 C C
ATOM 9366 NH1 ARG I 336 12.384 -9.718 -28.013 1.00 12.38 C N
ATOM 9367 NH2 ARG I 336 14.249 -10.681 -27.084 1.00 12.48 C N
ATOM 9368 C ARG 1 336 12.761 -3.833 -26.004 1.00 12.71 C C
ATOM 9369 O ARG 1 336 13.272 -3.932 -24.890 1.00 12.62 C O
ATOM 9370 N THR 1 337 11.501 -3.457 -26.186 1.00 13.70 C N
ATOM 9371 CA THR 1 337 10.696 -2.998 -25.065 1.00 14.91 C C
ATOM 9372 CB THR I 337 9.353 -2.405 -25.516 1.00 15.27 C C
ATOM 9373 OG1 THR I 337 9.571 -1.474 -26.584 1.00 16.65 C O
ATOM 9374 CG2 THR I 337 8.694 -1.678 -24.356 1.00 15.94 C C
ATOM 9375 C THR 1 337 10.438 -4.115 -24.064 1.00 15.16 C C
ATOM 9376 O THR 1 337 10.515 -3.902 -22.857 1.00 15.60 C O
ATOM 9377 N ASP 1 338 10.036 -5.277 -24.566 1.00 15.15 C N
ATOM 9378 CA ASP I 338 9.394 -6.289 -23.732 1.00 15.52 C C
ATOM 9379 CB ASP I 338 8.653 -7.306 -24.602 1.00 16.81 C C
ATOM 9380 CG ASP I 338 9.242 -7.417 -26.000 1.00 20.57 C C
ATOM 9381 OD1 ASP I 338 8.554 -7.950 -26.895 1.00 23.00 C O
ATOM 9382 OD2 ASP I 338 10.395 -6.981 -26.200 1.00 22.92 C O
ATOM 9383 C ASP 1 338 10.402 -7.004 -22.837 1.00 14.21 C C
ATOM 9384 O ASP 1 338 10.930 -8.057 -23.196 1.00 14.00 C O
ATOM 9385 N ARG 1 339 10.654 -6.432 -21.664 1.00 12.79 C N
ATOM 9386 CA ARG I 339 11.678 -6.949 -20.764 1.00 11.71 C C
ATOM 9387 CB ARG 1 339 12.488 -5.810 -20.163 1.00 11.73 C C
ATOM 9388 CG ARG 1 339 13.374 -5.080 -21.129 1.00 12.49 C C
ATOM 9389 CD ARG 1 339 14.312 -4.211 -20.346 1.00 13.24 C C
ATOM 9390 NE ARG I 339 14.580 -2.944 -21.005 1.00 12.04 C N
ATOM 9391 CZ ARG 1 339 15.717 -2.282 -20.858 1.00 11.74 C C
ATOM 9392 NH1 ARG I 339 16.664 -2.771 -20.072 1.00 13.43 C N
ATOM 9393 NH2 ARG I 339 15.904 -1.125 -21.475 1.00 9.80 C N
ATOM 9394 C ARG I 339 11.062 -7.727 -19.622 1.00 11.16 C C
ATOM 9395 O ARG 1 339 10.029 -7.326 -19.087 1.00 11.37 C O
ATOM 9396 N GLY 1 340 11.892 -8.572 -19.027 1.00 10.43 C N
ATOM 9397 CA GLY 1 340 11.574 -9.178 -17.749 1.00 9.52 C C
ATOM 9398 C GLY 1 340 11.463 -10.678 -17.876 1.00 8.80 C C
ATOM 9399 O GLY 1 340 12.269 -11.313 -18.555 1.00 8.56 C O
ATOM 9400 N TRP I 341 10.532 -11.257 -17.129 1.00 8.25 C N
ATOM 9401 CA TRP I 341 10.462 -12.699 -17.005 1.00 7.98 C C
ATOM 9402 CB TRP I 341 10.018 -13.097 -15.605 1.00 7.79 C C
ATOM 9403 CG TRP I 341 11.120 -13.020 -14.622 1.00 7.67 C C
ATOM 9404 CD 1 TRP I 341 11.382 -11.986 -13.775 1.00 8.12 C C
ATOM 9405 NE1 TRP I 341 12.511 -12.252 -13.042 1.00 8.60 C N ATOM 9406 CE2 T P I 341 13.037 -13.447 -13.459 1.00 7.57 C C
ATOM 9407 CD2 TRP I 341 12.217 -13.931 -14.495 1.00 7.52 C C
ATOM 9408 CE3 TRP I 341 12.541 -15.150 -15.098 1.00 7.86 C C
ATOM 9409 CZ3 TRP I 341 13.653 -15.837 -14.650 1.00 7.14 C C
ATOM 9410 CH2 TRP I 341 14.457 -15.323 -13.625 1.00 6.39 C C
ATOM 9411 CZ2 TRP I 341 14.164 -14.134 -13.017 1.00 7.30 C C
ATOM 9412 C TRP I 341 9.525 -13.288 -18.037 1.00 8.26 C C
ATOM 9413 O TRP 1 341 8.322 -13.022 -18.031 1.00 8.35 C O
ATOM 9414 N TYR 1 342 10.085 -14.100 -18.922 1.00 8.44 C N
ATOM 9415 CA TYR I 342 9.308 -15.102 -19.616 1.00 8.53 C C
ATOM 9416 CB TYR 1 342 9.755 -15.202 -21.069 1.00 8.43 C C
ATOM 9417 CG TYR I 342 9.687 -13.885 -21.793 1.00 9.17 C C
ATOM 9418 CD1 TYR I 342 10.592 -12.874 -21.499 1.00 10.32 C C
ATOM 9419 CE1 TYR I 342 10.474 -11.625 -22.068 1.00 10.99 C C
ATOM 9420 CZ TYR I 342 9.395 -11.349 -22.873 1.00 11.00 C C
ATOM 9421 OH TYR 1 342 9.267 -10.102 -23.435 1.00 12.82 C O
ATOM 9422 CE2 TYR I 342 8.433 -12.307 -23.105 1.00 10.67 C C
ATOM 9423 CD2 TYR I 342 8.569 -13.555 -22.542 1.00 10.41 C C
ATOM 9424 C TYR 1 342 9.469 -16.437 -18.925 1.00 8.64 C C
ATOM 9425 O TYR 1 342 10.376 -16.628 -18.115 1.00 8.40 C O
ATOM 9426 N CYS I 343 8.558 -17.351 -19.224 1.00 8.87 C N
ATOM 9427 CA CYS I 343 8.370 -18.516 -18.389 1.00 9.35 C C
ATOM 9428 CB CYS I 343 8.266 -18.116 -16.915 1.00 9.17 C C
ATOM 9429 SG CYS I 343 8.138 -19.512 -15.769 1.00 11.88 C S
ATOM 9430 C CYS 1 343 7.151 -19.312 -18.831 1.00 9.42 C C
ATOM 9431 O CYS 1 343 6.039 -18.788 -18.900 1.00 9.96 C O
ATOM 9432 N ASP 1 344 7.408 -20.545 -19.254 1.00 9.36 C N
ATOM 9433 CA ASP I 344 6.483 -21.302 -20.083 1.00 9.24 C C
ATOM 9434 CB ASP I 344 7.122 -22.628 -20.500 1.00 9.34 C C
ATOM 9435 CG ASP I 344 7.796 -22.551 -21.856 1.00 10.72 C C
ATOM 9436 OD1 ASP I 344 7.123 -22.161 -22.833 1.00 13.93 C O
ATOM 9437 OD2 ASP I 344 9.003 -22.864 -21.942 1.00 11.87 C O
ATOM 9438 C ASP 1 344 5.198 -21.576 -19.320 1.00 9.09 C C
ATOM 9439 O ASP 1 344 5.233 -22.061 -18.192 1.00 9.39 C O
ATOM 9440 N ASN I 345 4.067 -21.385 -19.988 1.00 9.13 C N
ATOM 9441 CA ASN I 345 2.801 -21.924 -19.510 1.00 9.52 C C
ATOM 9442 CB ASN I 345 1.770 -20.804 -19.361 1.00 9.61 C C
ATOM 9443 CG ASN I 345 0.742 -21.101 -18.293 1.00 9.21 C C
ATOM 9444 OD1 ASN I 345 1.075 -21.251 -17.118 1.00 6.21 C O
ATOM 9445 ND2 ASN I 345 -0.511 -21.247 -18.706 1.00 11.05 C N
ATOM 9446 C ASN 1 345 2.271 -23.022 -20.427 1.00 10.06 C C
ATOM 9447 O ASN 1 345 3.005 -23.546 -21.267 1.00 11.10 C O
ATOM 9448 N ALA I 346 1.017 -23.411 -20.223 1.00 9.74 C N
ATOM 9449 CA ALA 1 346 0.416 -24.492 -20.998 1.00 9.58 C C
ATOM 9450 CB ALA I 346 -1.062 -24.635 -20.650 1.00 9.60 C C
ATOM 9451 C ALA 1 346 0.593 -24.278 -22.502 1.00 9.66 C C
ATOM 9452 O ALA 1 346 -0.241 -23.639 -23.145 1.00 9.39 C O
ATOM 9453 N GLY I 347 1.655 -24.849 -23.065 1.00 10.04 C N
ATOM 9454 CA GLY 1 347 1.836 -24.857 -24.513 1.00 10.68 C C
ATOM 9455 C GLY 1 347 1.879 -23.454 -25.085 1.00 10.90 C C
ATOM 9456 O GLY 1 347 1.661 -23.251 -26.280 1.00 11.46 C O
ATOM 9457 N SER I 348 2.016 -22.477 -24.193 1.00 10.30 C N
ATOM 9458 CA SER I 348 2.256 -21.088 -24.567 1.00 9.94 C C
ATOM 9459 CB SER I 348 0.933 -20.322 -24.613 1.00 9.88 C C
ATOM 9460 OG SER I 348 0.000 -20.969 -25.461 1.00 10.09 C O
ATOM 9461 C SER 1 348 3.194 -20.462 -23.538 1.00 9.60 C C
ATOM 9462 O SER I 348 3.700 -21.157 -22.660 1.00 9.59 C O
ATOM 9463 N VAL 1 349 3.494 -19.178 -23.689 1.00 9.54 C N
ATOM 9464 CA VAL 1 349 4.452 -18.532 -22.800 1.00 9.56 C C
ATOM 9465 CB VAL I 349 5.700 -18.047 -23.558 1.00 9.28 C C ATOM 9466 CGI VAL I 349 6.722 -17.476 -22.589 1.00 9.24 C c
ATOM 9467 CG2 VAL I 349 6.303 -19.183 -24.370 1.00 9.94 c c
ATOM 9468 C VAL I 349 3.832 -17.367 -22.041 1.00 9.59 c c
ATOM 9469 O VAL I 349 3.179 -16.506 -22.631 1.00 9.69 c o
ATOM 9470 N SE I 350 4.073 -17.326 -20.735 1.00 9.93 c N
ATOM 9471 CA SE I 350 3.559 -16.252 -19.896 1.00 10.44 c c
ATOM 9472 CB SE I 350 2.926 -16.815 -18.620 1.00 10.04 c c
ATOM 9473 OG SE I 350 1.578 -17.196 -18.841 1.00 8.41 c o
ATOM 9474 C SER I 350 4.629 -15.218 -19.557 1.00 11.45 c c
ATOM 9475 O SER I 350 5.746 -15.561 -19.168 1.00 11.58 c o
ATOM 9476 N PHE I 351 4.259 -13.948 -19.679 1.00 12.28 c N
ATOM 9477 CA PHE I 351 5.200 -12.847 -19.543 1.00 13.04 c c
ATOM 9478 CB PHE I 351 5.320 -12.089 -20.867 1.00 12.87 c c
ATOM 9479 CG PHE I 351 6.094 -10.809 -20.763 1.00 13.52 c c
ATOM 9480 CD1 PHE I 351 7.344 -10.788 -20.172 1.00 13.76 c c
ATOM 9481 CE1 PHE I 351 8.066 -9.613 -20.085 1.00 14.10 c c
ATOM 9482 CZ PHE I 351 7.541 -8.442 -20.588 1.00 14.07 c c
ATOM 9483 CE2 PHE I 351 6.305 -8.452 -21.197 1.00 14.14 c c
ATOM 9484 CD2 PHE I 351 5.580 -9.629 -21.270 1.00 13.92 c c
ATOM 9485 C PHE I 351 4.742 -11.899 -18.441 1.00 13.84 c c
ATOM 9486 O PHE I 351 3.579 -11.499 -18.394 1.00 13.96 c o
ATOM 9487 N PHE I 352 5.655 -11.574 -17.534 1.00 14.72 c N
ATOM 9488 CA PHE I 352 5.344 -10.699 -16.412 1.00 15.98 c c
ATOM 9489 CB PHE I 352 5.570 -11.435 -15.093 1.00 15.75 c c
ATOM 9490 CG PHE I 352 5.295 -12.909 -15.169 1.00 15.51 c c
ATOM 9491 CD1 PHE I 352 6.188 -13.762 -15.803 1.00 15.05 c c
ATOM 9492 CE1 PHE I 352 5.926 -15.116 -15.902 1.00 14.05 c c
ATOM 9493 CZ PHE I 352 4.745 -15.624 -15.402 1.00 13.28 c c
ATOM 9494 CE2 PHE I 352 3.833 -14.777 -14.796 1.00 13.71 c c
ATOM 9495 CD2 PHE I 352 4.099 -13.425 -14.704 1.00 14.94 c c
ATOM 9496 C PHE I 352 6.195 -9.438 -16.453 1.00 17.56 c c
ATOM 9497 O PHE I 352 7.419 -9.509 -16.360 1.00 17.74 c o
ATOM 9498 N PRO I 353 5.541 -8.271 -16.525 1.00 19.05 c N
ATOM 9499 CA PRO I 353 6.188 -7.074 -17.055 1.00 20.40 c c
ATOM 9500 CB PRO I 353 5.010 -6.146 -17.365 1.00 20.26 c c
ATOM 9501 CG PRO I 353 3.839 -7.052 -17.522 1.00 19.71 c c
ATOM 9502 CD PRO I 353 4.073 -8.155 -16.545 1.00 18.97 c c
ATOM 9503 C PRO I 353 7.136 -6.408 -16.058 1.00 21.94 c c
ATOM 9504 O PRO I 353 8.087 -5.745 -16.470 1.00 22.29 c o
ATOM 9505 N GLN I 354 6.858 -6.544 -14.763 1.00 23.38 c N
ATOM 9506 CA GLN I 354 7.646 -5.847 -13.743 1.00 24.64 c c
ATOM 9507 CB GLN I 354 6.943 -4.569 -13.274 1.00 24.93 c c
ATOM 9508 CG GLN I 354 5.458 -4.509 -13.587 1.00 26.00 c c
ATOM 9509 CD GLN I 354 4.646 -5.481 -12.756 1.00 25.92 c c
ATOM 9510 OE1 GLN I 354 4.710 -5.474 -11.527 1.00 25.67 c o
ATOM 9511 NE2 GLN I 354 3.870 -6.324 -13.427 1.00 24.27 c N
ATOM 9512 C GLN I 354 8.048 -6.707 -12.543 1.00 24.85 c c
ATOM 9513 O GLN I 354 7.280 -7.556 -12.088 1.00 24.51 c o
ATOM 9514 N ALA I 355 9.200 -6.384 -11.959 1.00 25.22 c N
ATOM 9515 CA ALA I 355 9.818 -7.215 -10.926 1.00 25.34 c c
ATOM 9516 CB ALA I 355 10.949 -6.458 -10.245 1.00 25.09 c c
ATOM 9517 C ALA I 355 8.809 -7.711 -9.892 1.00 24.92 c c
ATOM 9518 O ALA I 355 8.679 -8.915 -9.669 1.00 25.23 c o
ATOM 9519 N GLU I 356 8.278 -6.771 -9.115 1.00 23.93 c N
ATOM 9520 CA GLU I 356 7.089 -6.998 -8.295 1.00 22.77 c c
ATOM 9521 CB GLU I 356 5.993 -5.995 -8.658 1.00 23.22 c c
ATOM 9522 CG GLU I 356 6.412 -4.545 -8.500 1.00 26.33 c c
ATOM 9523 CD GLU I 356 7.250 -4.314 -7.258 1.00 30.93 c c
ATOM 9524 OE1 GLU I 356 8.490 -4.231 -7.380 1.00 31.97 c o
ATOM 9525 OE2 GLU I 356 6.668 -4.227 -6.156 1.00 32.21 c o ATOM 9526 C GLU I 356 6.547 -8.419 -8.377 1.00 21.31 C c
ATOM 9527 O GLU I 356 6.338 -9.070 -7.354 1.00 21.01 c o
ATOM 9528 N TH I 357 6.137 -8.809 -9.577 1.00 19.51 c N
ATOM 9529 CA TH I 357 5.358 -10.023 -9.766 1.00 17.55 c c
ATOM 9530 CB TH I 357 4.829 -10.115 -11.207 1.00 17.30 c c
ATOM 9531 OG1 THR I 357 5.071 -8.873 -11.882 1.00 17.32 c o
ATOM 9532 CG2 THR I 357 3.335 -10.387 -11.203 1.00 17.72 c : c
ATOM 9533 C THR I 357 6.178 -11.268 -9.433 1.00 16.62 c c
ATOM 9534 O THR I 357 5.631 -12.286 -9.008 1.00 17.29 c o
ATOM 9535 N CYS I 358 7.498 -11.146 -9.526 1.00 14.88 c N
ATOM 9536 CA CYS I 358 8.365 -12.317 -9.566 1.00 13.15 c c
ATOM 9537 CB CYS I 358 8.955 -12.501 -10.961 1.00 13.04 c c
ATOM 9538 SG CYS I 358 7.735 -12.899 -12.228 1.00 14.02 c s
ATOM 9539 C CYS I 358 9.478 -12.255 -8.529 1.00 12.08 c c
ATOM 9540 O CYS I 358 10.186 -11.252 -8.417 1.00 12.15 c o
ATOM 9541 N LYS I 359 9.640 -13.345 -7.788 1.00 11.35 c N
ATOM 9542 CA LYS I 359 10.793 -13.519 -6.918 1.00 11.01 c c
ATOM 9543 CB LYS I 359 10.349 -13.675 -5.460 1.00 11.16 c c
ATOM 9544 CG LYS I 359 8.858 -13.470 -5.229 1.00 13.28 c c
ATOM 9545 CD LYS I 359 8.607 -12.427 -4.150 1.00 16.11 c c
ATOM 9546 CE LYS I 359 7.124 -12.287 -3.850 1.00 17.91 c c
ATOM 9547 NZ LYS I 359 6.818 -11.012 -3.145 1.00 20.99 c N
ATOM 9548 C LYS I 359 11.592 -14.739 -7.349 1.00 10.46 c c
ATOM 9549 O LYS I 359 11.091 -15.589 -8.085 1.00 10.70 c o
ATOM 9550 N VAL I 360 12.791 -14.880 -6.798 1.00 9.99 c N
ATOM 9551 CA VAL I 360 13.720 -15.885 -7.282 1.00 9.84 c c
ATOM 9552 CB VAL I 360 14.452 -15.412 -8.541 1.00 9.42 c c
ATOM 9553 CGI VAL I 360 15.135 -14.066 -8.288 1.00 10.07 c c
ATOM 9554 CG2 VAL I 360 15.454 -16.473 -8.996 1.00 9.56 c c
ATOM 9555 C VAL I 360 14.738 -16.297 -6.229 1.00 9.98 c c
ATOM 9556 O VAL I 360 15.380 -15.457 -5.598 1.00 9.96 c o
ATOM 9557 N GLN I 361 14.900 -17.604 -6.071 1.00 10.39 c N
ATOM 9558 CA GLN I 361 15.781 -18.150 -5.052 1.00 11.53 c c
ATOM 9559 CB GLN I 361 14.966 -18.692 -3.880 1.00 12.03 c c
ATOM 9560 CG GLN I 361 15.810 -19.254 -2.750 1.00 16.44 c c
ATOM 9561 CD GLN I 361 15.388 -18.722 -1.398 1.00 25.16 c c
ATOM 9562 OE1 GLN I 361 14.773 -19.434 -0.604 1.00 29.01 c : o
ATOM 9563 NE2 GLN I 361 15.686 -17.453 -1.141 1.00 27.20 c : N
ATOM 9564 C GLN I 361 16.613 -19.271 -5.641 1.00 11.15 c c
ATOM 9565 O GLN I 361 16.114 -20.375 -5.854 1.00 11.80 c o
ATOM 9566 N SER I 362 17.877 -18.986 -5.925 1.00 10.90 c N
ATOM 9567 CA SER I 362 18.671 -19.921 -6.695 1.00 10.30 c c
ATOM 9568 CB SER I 362 18.610 -21.302 -6.040 1.00 10.47 c c
ATOM 9569 OG SER I 362 19.659 -22.138 -6.491 1.00 11.17 c o
ATOM 9570 C SER I 362 18.088 -19.980 -8.103 1.00 9.58 c c
ATOM 9571 O SER I 362 17.759 -18.946 -8.683 1.00 9.48 c o
ATOM 9572 N ASN I 363 17.806 -21.188 -8.577 1.00 9.12 c N
ATOM 9573 CA ASN I 363 17.229 -21.365 -9.904 1.00 8.73 c c
ATOM 9574 CB ASN I 363 17.821 -22.602 -10.568 1.00 9.01 c c
ATOM 9575 CG ASN I 363 17.547 -23.864 -9.781 1.00 9.29 c c
ATOM 9576 OD1 ASN I 363 16.903 -23.826 -8.732 1.00 9.82 c o
ATOM 9577 ND2 ASN I 363 17.981 -25.000 -10.314 1.00 10.08 C N
ATOM 9578 C ASN I 363 15.716 -21.503 -9.827 1.00 8.12 c c
ATOM 9579 O ASN I 363 15.084 -22.042 -10.736 1.00 8.10 c o
ATOM 9580 N ARG I 364 15.168 -21.165 -8.665 1.00 7.20 c N
ATOM 9581 CA ARG I 364 13.731 -21.222 -8.445 1.00 6.82 c c
ATOM 9582 CB ARG I 364 13.427 -21.658 -7.012 1.00 6.91 c c
ATOM 9583 CG ARG I 364 12.287 -22.649 -6.908 1.00 7.92 c c
ATOM 9584 CD ARG I 364 12.520 -23.817 -7.843 1.00 8.20 c c
ATOM 9585 NE ARG I 364 11.374 -24.061 -8.711 1.00 8.70 c N ATOM 9586 CZ A G I 364 11.056 -25.255 -9.196 1.00 8.88 C C
ATOM 9587 NH1 ARG I 364 11.800 -26.309 -8.894 1.00 8.57 C N
ATOM 9588 NH2 ARG I 364 9.976 -25.403 -9.950 1.00 10.59 C N
ATOM 9589 C ARG I 364 13.110 -19.861 -8.694 1.00 6.58 C C
ATOM 9590 O ARG I 364 13.540 -18.861 -8.121 1.00 6.65 C O
ATOM 9591 N VAL I 365 12.031 -19.846 -9.466 1.00 6.64 C N
ATOM 9592 CA VAL I 365 11.325 -18.609 -9.756 1.00 6.54 C C
ATOM 9593 CB VAL I 365 11.399 -18.261 -11.254 1.00 5.95 C C
ATOM 9594 CGI VAL I 365 10.374 -17.196 -11.608 1.00 5.48 C C
ATOM 9595 CG2 VAL I 365 12.801 -17.804 -11.623 1.00 6.22 C C
ATOM 9596 C VAL 1 365 9.866 -18.723 -9.335 1.00 7.35 C C
ATOM 9597 O VAL 1 365 9.271 -19.799 -9.416 1.00 8.33 C O
ATOM 9598 N PHE I 366 9.309 -17.619 -8.843 1.00 7.37 C N
ATOM 9599 CA PHE I 366 7.919 -17.584 -8.401 1.00 7.44 C C
ATOM 9600 CB PHE I 366 7.840 -17.604 -6.875 1.00 7.30 C C
ATOM 9601 CG PHE I 366 8.426 -18.834 -6.255 1.00 6.70 C C
ATOM 9602 CD 1 PHE I 366 9.799 -18.991 -6.163 1.00 6.70 C C
ATOM 9603 CE1 PHE I 366 10.345 -20.120 -5.588 1.00 5.94 C C
ATOM 9604 CZ PHE I 366 9.520 -21.083 -5.055 1.00 5.71 C C
ATOM 9605 CE2 PHE I 366 8.149 -20.934 -5.130 1.00 5.96 C C
ATOM 9606 CD2 PHE I 366 7.609 -19.805 -5.710 1.00 6.52 C C
ATOM 9607 C PHE 1 366 7.236 -16.335 -8.919 1.00 7.45 C C
ATOM 9608 O PHE I 366 7.530 -15.225 -8.476 1.00 7.45 C O
ATOM 9609 N CYS I 367 6.282 -16.524 -9.819 1.00 8.00 C N
ATOM 9610 CA CYS I 367 5.626 -15.400 -10.450 1.00 8.90 C C
ATOM 9611 CB CYS I 367 5.985 -15.338 -11.934 1.00 9.46 C C
ATOM 9612 SG CYS I 367 7.712 -14.929 -12.259 1.00 10.79 C S
ATOM 9613 C CYS 1 367 4.121 -15.484 -10.268 1.00 9.09 C C
ATOM 9614 O CYS I 367 3.591 -16.493 -9.799 1.00 9.24 C O
ATOM 9615 N ASP 1 368 3.449 -14.382 -10.568 1.00 9.54 C N
ATOM 9616 CA ASP I 368 2.034 -14.255 -10.285 1.00 10.55 C C
ATOM 9617 CB ASP I 368 1.792 -13.067 -9.349 1.00 10.53 C C
ATOM 9618 CG ASP I 368 0.421 -13.102 -8.698 1.00 11.11 C C
ATOM 9619 OD1 ASP I 368 -0.574 -13.335 -9.415 1.00 11.42 C O
ATOM 9620 OD2 ASP I 368 0.323 -12.765 -7.499 1.00 11.35 C O
ATOM 9621 C ASP 1 368 1.266 -14.073 -11.590 1.00 11.45 C C
ATOM 9622 O ASP 1 368 1.418 -13.061 -12.274 1.00 12.05 C O
ATOM 9623 N THR 1 369 0.563 -15.122 -12.003 1.00 12.41 C N
ATOM 9624 CA THR 1 369 -0.399 -15.013 -13.089 1.00 13.00 C C
ATOM 9625 CB THR 1 369 -1.513 -16.063 -12.953 1.00 12.69 C C
ATOM 9626 OG1 THR I 369 -0.935 -17.374 -12.929 1.00 11.72 C O
ATOM 9627 CG2 THR I 369 -2.488 -15.962 -14.115 1.00 13.33 C C
ATOM 9628 C THR 1 369 -1.034 -13.632 -13.093 1.00 14.13 C C
ATOM 9629 O THR 1 369 -0.895 -12.874 -14.051 1.00 14.72 C O
ATOM 9630 N MET 1 370 -1.675 -13.289 -11.984 1.00 15.25 C N
ATOM 9631 CA MET 1 370 -2.681 -12.240 -11.975 1.00 16.60 C C
ATOM 9632 CB MET 1 370 -2.538 -11.361 -10.734 1.00 17.42 C C
ATOM 9633 CG MET I 370 -3.744 -11.411 -9.811 1.00 20.31 C C
ATOM 9634 SD MET 1 370 -5.284 -10.974 -10.642 1.00 26.43 C S
ATOM 9635 CE MET I 370 -5.320 -12.185 -11.963 1.00 24.07 C C
ATOM 9636 C MET 1 370 -2.700 -11.396 -13.249 1.00 16.54 C C
ATOM 9637 O MET 1 370 -3.707 -11.367 -13.953 1.00 16.74 C O
ATOM 9638 N ASN I 371 -1.610 -10.691 -13.540 1.00 16.35 C N
ATOM 9639 CA ASN I 371 -1.614 -9.772 -14.680 1.00 16.07 C C
ATOM 9640 CB ASN I 371 -1.375 -8.326 -14.232 1.00 16.41 C C
ATOM 9641 CG ASN I 371 -2.619 -7.690 -13.634 1.00 16.71 C C
ATOM 9642 OD1 ASN I 371 -3.501 -7.228 -14.356 1.00 15.75 C O
ATOM 9643 ND2 ASN I 371 -2.722 -7.724 -12.310 1.00 17.76 C N
ATOM 9644 C ASN I 371 -0.698 -10.167 -15.842 1.00 15.55 C C
ATOM 9645 O ASN I 371 -0.650 -9.478 -16.862 1.00 15.84 C O ATOM 9646 N SE I 372 -0.166 -11.383 -15.771 1.00 14.76 C N
ATOM 9647 CA SE I 372 0.540 -11.990 -16.894 1.00 13.91 c c
ATOM 9648 CB SE I 372 0.561 -13.512 -16.746 1.00 14.04 c c
ATOM 9649 OG SE I 372 -0.696 -14.071 -17.084 1.00 15.09 c o
ATOM 9650 C SER I 372 -0.071 -11.614 -18.242 1.00 13.07 c c
ATOM 9651 O SER I 372 -1.291 -11.511 -18.373 1.00 13.02 c o
ATOM 9652 N LEU I 373 0.781 -11.525 -19.263 1.00 12.23 c N
ATOM 9653 CA LEU I 373 0.352 -11.621 -20.658 1.00 11.45 c c
ATOM 9654 CB LEU I 373 0.999 -10.504 -21.485 1.00 11.43 c c
ATOM 9655 CG LEU I 373 0.250 -9.176 -21.636 1.00 11.04 c c
ATOM 9656 CD1 LEU I 373 -0.580 -8.867 -20.406 1.00 11.76 c c
ATOM 9657 CD2 LEU I 373 1.213 -8.035 -21.928 1.00 10.49 c c
ATOM 9658 C LEU I 373 0.727 -12.982 -21.247 1.00 11.17 c c
ATOM 9659 O LEU I 373 1.819 -13.492 -21.000 1.00 11.27 c o
ATOM 9660 N THR I 374 -0.164 -13.546 -22.056 1.00 10.70 c N
ATOM 9661 CA THR I 374 0.062 -14.869 -22.633 1.00 10.23 c c
ATOM 9662 CB THR I 374 -1.187 -15.768 -22.531 1.00 10.24 c c
ATOM 9663 OG1 THR I 374 -1.999 -15.346 -21.429 1.00 11.25 c o
ATOM 9664 CG2 THR I 374 -0.785 -17.224 -22.338 1.00 10.52 c : c
ATOM 9665 C THR I 374 0.481 -14.772 -24.091 1.00 9.54 c c
ATOM 9666 O THR I 374 -0.164 -14.097 -24.893 1.00 9.70 c o
ATOM 9667 N LEU I 375 1.576 -15.444 -24.422 1.00 8.83 c N
ATOM 9668 CA LEU I 375 2.236 -15.253 -25.704 1.00 7.83 c c
ATOM 9669 CB LEU I 375 3.470 -14.361 -25.547 1.00 7.38 c c
ATOM 9670 CG LEU I 375 3.309 -13.047 -24.780 1.00 5.06 c c
ATOM 9671 CD1 LEU I 375 4.669 -12.411 -24.533 1.00 2.41 c c
ATOM 9672 CD2 LEU I 375 2.397 -12.098 -25.535 1.00 4.31 c c
ATOM 9673 C LEU I 375 2.644 -16.600 -26.283 1.00 7.79 c c
ATOM 9674 O LEU I 375 2.703 -17.598 -25.565 1.00 7.92 c o
ATOM 9675 N PRO I 376 2.914 -16.629 -27.595 1.00 7.51 c N
ATOM 9676 CA PRO I 376 3.325 -17.826 -28.323 1.00 7.90 c c
ATOM 9677 CB PRO I 376 2.852 -17.538 -29.748 1.00 7.90 c c
ATOM 9678 CG PRO I 376 2.913 -16.062 -29.858 1.00 7.97 c c
ATOM 9679 CD PRO I 376 2.537 -15.534 -28.505 1.00 7.40 c c
ATOM 9680 C PRO I 376 4.838 -18.023 -28.310 1.00 8.35 c c
ATOM 9681 O PRO I 376 5.589 -17.062 -28.484 1.00 8.71 c o
ATOM 9682 N SER I 377 5.263 -19.283 -28.263 1.00 9.11 c N
ATOM 9683 CA SER I 377 6.682 -19.622 -28.207 1.00 9.91 c c
ATOM 9684 CB SER I 377 6.880 -21.137 -28.330 1.00 10.23 c c
ATOM 9685 OG SER I 377 5.713 -21.842 -27.939 1.00 10.90 c o
ATOM 9686 C SER I 377 7.438 -18.911 -29.319 1.00 10.14 c c
ATOM 9687 O SER I 377 8.660 -19.024 -29.425 1.00 10.08 c o
ATOM 9688 N GLU I 378 6.683 -18.286 -30.215 1.00 10.71 c N
ATOM 9689 CA GLU I 378 7.256 -17.563 -31.339 1.00 11.40 c c
ATOM 9690 CB GLU I 378 6.177 -17.256 -32.379 1.00 11.65 c c
ATOM 9691 CG GLU I 378 5.858 -18.418 -33.312 1.00 13.46 c c
ATOM 9692 CD GLU I 378 5.249 -19.608 -32.588 1.00 16.20 c c
ATOM 9693 OE1 GLU I 378 4.999 -19.505 -31.368 1.00 15.73 c o
ATOM 9694 OE2 GLU I 378 4.989 -20.636 -33.250 1.00 18.38 c o
ATOM 9695 C GLU I 378 7.922 -16.274 -30.873 1.00 11.27 c c
ATOM 9696 O GLU I 378 8.776 -15.722 -31.567 1.00 11.28 c o
ATOM 9697 N VAL I 379 7.570 -15.827 -29.672 1.00 11.31 c N
ATOM 9698 CA VAL I 379 8.268 -14.708 -29.056 1.00 11.59 c c
ATOM 9699 CB VAL I 379 7.849 -14.504 -27.591 1.00 11.27 c c
ATOM 9700 CGI VAL I 379 8.894 -13.674 -26.858 1.00 11.60 c : c
ATOM 9701 CG2 VAL I 379 6.486 -13.833 -27.520 1.00 11.54 c : c
ATOM 9702 C VAL I 379 9.779 -14.907 -29.124 1.00 12.16 c c
ATOM 9703 O VAL I 379 10.533 -13.943 -29.255 1.00 12.51 c o
ATOM 9704 N ASN I 380 10.219 -16.158 -29.030 1.00 12.98 c N
ATOM 9705 CA ASN I 380 11.637 -16.453 -28.854 1.00 14.00 c c ATOM 9706 CB ASN I 380 11.854 -17.947 -28.579 1.00 14.59 C C
ATOM 9707 CG ASN 1 380 11.318 -18.381 -27.224 1.00 17.09 C C
ATOM 9708 OD1 ASN I 380 12.070 -18.488 -26.256 1.00 20.41 C O
ATOM 9709 ND2 ASN I 380 10.045 -18.763 -27.186 1.00 18.86 C N
ATOM 9710 C ASN 1 380 12.477 -16.006 -30.051 1.00 13.96 C C
ATOM 9711 O ASN 1 380 13.619 -15.576 -29.890 1.00 14.38 C O
ATOM 9712 N LEU I 381 11.925 -16.159 -31.252 1.00 13.61 C N
ATOM 9713 CA LEU I 381 12.638 -15.798 -32.475 1.00 13.72 C C
ATOM 9714 CB LEU I 381 11.742 -15.996 -33.698 1.00 13.79 C C
ATOM 9715 CG LEU I 381 10.720 -17.130 -33.607 1.00 14.92 C C
ATOM 9716 CD1 LEU I 381 9.817 -17.138 -34.830 1.00 15.56 C C
ATOM 9717 CD2 LEU I 381 11.421 -18.470 -33.446 1.00 15.78 C C
ATOM 9718 C LEU 1 381 13.093 -14.349 -32.401 1.00 13.62 C C
ATOM 9719 O LEU 1 381 14.017 -13.934 -33.100 1.00 13.57 C O
ATOM 9720 N CYS 1 382 12.473 -13.607 -31.494 1.00 13.47 C N
ATOM 9721 CA CYS I 382 12.727 -12.187 -31.357 1.00 13.57 C C
ATOM 9722 CB CYS I 382 11.613 -11.538 -30.545 1.00 13.62 C C
ATOM 9723 SG CYS I 382 10.346 -10.770 -31.551 1.00 15.64 C S
ATOM 9724 C CYS 1 382 14.073 -11.928 -30.696 1.00 13.33 C C
ATOM 9725 O CYS 1 382 14.690 -10.887 -30.923 1.00 13.57 C O
ATOM 9726 N ASN 1 383 14.565 -12.914 -29.948 1.00 13.21 C N
ATOM 9727 CA ASN 1 383 15.925 -12.865 -29.415 1.00 13.22 C C
ATOM 9728 CB ASN 1 383 16.191 -14.054 -28.491 1.00 13.18 C C
ATOM 9729 CG ASN 1 383 15.154 -14.186 -27.400 1.00 13.42 C C
ATOM 9730 OD1 ASN I 383 14.774 -13.202 -26.769 1.00 13.68 C O
ATOM 9731 ND2 ASN I 383 14.660 -15.402 -27.199 1.00 14.32 C N
ATOM 9732 C ASN 1 383 16.959 -12.845 -30.530 1.00 13.28 C C
ATOM 9733 O ASN 1 383 18.081 -12.374 -30.344 1.00 13.50 C O
ATOM 9734 N VAL I 384 16.605 -13.451 -31.657 1.00 13.24 C N
ATOM 9735 CA VAL I 384 17.532 -13.584 -32.767 1.00 13.29 C C
ATOM 9736 CB VAL I 384 17.484 -14.992 -33.387 1.00 13.28 C C
ATOM 9737 CGI VAL I 384 18.046 -14.970 -34.800 1.00 13.73 C C
ATOM 9738 CG2 VAL I 384 18.251 -15.977 -32.518 1.00 12.76 C C
ATOM 9739 C VAL 1 384 17.292 -12.529 -33.842 1.00 13.57 C C
ATOM 9740 O VAL 1 384 18.239 -12.070 -34.480 1.00 13.31 C O
ATOM 9741 N ASP 1 385 16.038 -12.140 -34.049 1.00 14.07 C N
ATOM 9742 CA ASP I 385 15.711 -11.380 -35.249 1.00 14.61 C C
ATOM 9743 CB ASP I 385 15.049 -12.246 -36.318 1.00 14.71 C C
ATOM 9744 CG ASP I 385 15.608 -11.980 -37.701 1.00 16.69 C C
ATOM 9745 OD1 ASP I 385 16.308 -10.959 -37.872 1.00 18.63 C O
ATOM 9746 OD2 ASP I 385 15.367 -12.800 -38.612 1.00 19.10 C O
ATOM 9747 C ASP 1 385 15.014 -10.029 -35.092 1.00 14.63 C C
ATOM 9748 O ASP 1 385 15.412 -9.054 -35.728 1.00 14.34 C O
ATOM 9749 N ILE 1 386 13.937 -9.980 -34.314 1.00 14.54 C N
ATOM 9750 CA ILE I 386 13.154 -8.752 -34.212 1.00 14.46 C C
ATOM 9751 CB ILE I 386 14.074 -7.521 -34.137 1.00 13.83 C C
ATOM 9752 CGI ILE I 386 14.932 -7.584 -32.875 1.00 13.44 C C
ATOM 9753 CD1 ILE I 386 16.315 -7.018 -33.048 1.00 12.39 C C
ATOM 9754 CG2 ILE I 386 13.253 -6.241 -34.161 1.00 13.51 C C
ATOM 9755 C ILE 1 386 12.274 -8.602 -35.443 1.00 14.73 C C
ATOM 9756 O ILE 1 386 11.048 -8.692 -35.369 1.00 14.68 C O
ATOM 9757 N PHE 1 387 12.917 -8.301 -36.564 1.00 14.71 C N
ATOM 9758 CA PHE I 387 12.294 -8.428 -37.868 1.00 14.78 C C
ATOM 9759 CB PHE I 387 12.993 -7.528 -38.876 1.00 14.77 C C
ATOM 9760 CG PHE I 387 13.269 -6.154 -38.354 1.00 14.75 C C
ATOM 9761 CD1 PHE I 387 14.538 -5.818 -37.909 1.00 15.03 C C
ATOM 9762 CE1 PHE I 387 14.790 -4.572 -37.366 1.00 14.62 C C
ATOM 9763 CZ PHE I 387 13.743 -3.702 -37.131 1.00 14.55 C C
ATOM 9764 CE2 PHE I 387 12.452 -4.074 -37.463 1.00 14.68 C C
ATOM 9765 CD2 PHE I 387 12.219 -5.303 -38.052 1.00 14.61 C C ATOM 9766 C PHE I 387 12.291 -9.864 -38.352 1.00 14.91 C c
ATOM 9767 O PHE I 387 13.339 -10.461 -38.604 1.00 14.86 c o
ATOM 9768 N ASN I 388 11.102 -10.448 -38.325 1.00 15.11 c N
ATOM 9769 CA ASN I 388 10.866 -11.776 -38.850 1.00 15.38 c c
ATOM 9770 CB ASN I 388 11.522 -12.817 -37.947 1.00 14.86 c c
ATOM 9771 CG ASN I 388 11.029 -12.733 -36.519 1.00 14.86 c c
ATOM 9772 OD1 ASN I 388 10.004 -13.318 -36.170 1.00 12.80 c o
ATOM 9773 ND2 ASN I 388 11.708 -11.934 -35.707 1.00 15.97 C N
ATOM 9774 C ASN I 388 9.363 -11.982 -38.843 1.00 16.11 c c
ATOM 9775 O ASN I 388 8.688 -11.570 -37.902 1.00 15.92 c o
ATOM 9776 N PRO I 389 8.817 -12.450 -39.969 1.00 16.99 c N
ATOM 9777 CA PRO I 389 7.464 -12.988 -39.920 1.00 17.40 c c
ATOM 9778 CB PRO I 389 7.376 -13.815 -41.204 1.00 17.72 c c
ATOM 9779 CG PRO I 389 8.776 -14.223 -41.477 1.00 17.47 c c
ATOM 9780 CD PRO I 389 9.618 -13.063 -41.043 1.00 17.05 c c
ATOM 9781 C PRO I 389 7.304 -13.894 -38.706 1.00 17.86 c c
ATOM 9782 O PRO I 389 8.297 -14.397 -38.181 1.00 18.45 c o
ATOM 9783 N LYS I 390 6.068 -14.106 -38.269 1.00 17.97 c N
ATOM 9784 CA LYS I 390 5.813 -14.937 -37.098 1.00 18.06 c c
ATOM 9785 CB LYS I 390 6.986 -15.889 -36.844 1.00 17.92 c c
ATOM 9786 CG LYS I 390 7.066 -17.065 -37.806 1.00 18.58 c c
ATOM 9787 CD LYS I 390 6.331 -18.283 -37.264 1.00 20.61 c c
ATOM 9788 CE LYS I 390 6.758 -19.556 -37.982 1.00 21.48 c c
ATOM 9789 NZ LYS I 390 6.197 -19.645 -39.360 1.00 23.16 c N
ATOM 9790 C LYS I 390 5.557 -14.087 -35.858 1.00 18.01 c c
ATOM 9791 O LYS I 390 4.552 -14.267 -35.171 1.00 18.43 c o
ATOM 9792 N TYR I 391 6.490 -13.192 -35.548 1.00 17.68 c N
ATOM 9793 CA TYR I 391 6.267 -12.216 -34.492 1.00 17.33 c c
ATOM 9794 CB TYR I 391 7.026 -12.599 -33.224 1.00 17.42 c c
ATOM 9795 CG TYR I 391 6.220 -12.376 -31.971 1.00 17.27 c c
ATOM 9796 CD1 TYR I 391 4.863 -12.657 -31.951 1.00 17.29 c c
ATOM 9797 CE1 TYR I 391 4.108 -12.437 -30.822 1.00 17.32 c c
ATOM 9798 CZ TYR I 391 4.678 -11.809 -29.739 1.00 16.51 c c
ATOM 9799 OH TYR I 391 3.934 -11.601 -28.602 1.00 16.65 c o
ATOM 9800 CE2 TYR I 391 6.005 -11.441 -29.765 1.00 16.52 c c
ATOM 9801 CD2 TYR I 391 6.756 -11.689 -30.893 1.00 17.24 c c
ATOM 9802 C TYR I 391 6.623 -10.796 -34.910 1.00 17.43 c c
ATOM 9803 O TYR I 391 7.786 -10.491 -35.175 1.00 17.70 c o
ATOM 9804 N ASP I 392 5.647 -9.899 -34.813 1.00 17.56 c N
ATOM 9805 CA ASP I 392 5.944 -8.487 -34.609 1.00 17.69 c c
ATOM 9806 CB ASP I 392 4.779 -7.590 -35.045 1.00 17.89 c c
ATOM 9807 CG ASP I 392 3.556 -8.380 -35.472 1.00 18.86 c c
ATOM 9808 OD1 ASP I 392 2.911 -8.993 -34.596 1.00 20.34 c o
ATOM 9809 OD2 ASP I 392 3.162 -8.272 -36.653 1.00 18.51 c o
ATOM 9810 C ASP I 392 6.342 -8.188 -33.169 1.00 17.11 C i c
ATOM 9811 O ASP I 392 5.674 -8.609 -32.222 1.00 17.04 c o
ATOM 9812 N CYS I 393 7.356 -7.342 -33.026 1.00 16.33 c N
ATOM 9813 CA CYS I 393 8.347 -7.491 -31.975 1.00 16.17 c c
ATOM 9814 CB CYS I 393 9.656 -8.022 -32.554 1.00 16.11 c c
ATOM 9815 SG CYS I 393 10.738 -8.792 -31.342 1.00 20.23 c s
ATOM 9816 C CYS I 393 8.587 -6.139 -31.330 1.00 15.37 c c
ATOM 9817 O CYS I 393 9.066 -5.209 -31.980 1.00 15.15 c o
ATOM 9818 N LYS I 394 8.077 -5.982 -30.115 1.00 14.91 c N
ATOM 9819 CA LYS I 394 7.988 -4.668 -29.502 1.00 14.50 c c
ATOM 9820 CB LYS I 394 7.163 -4.724 -28.214 1.00 14.60 c c
ATOM 9821 CG LYS I 394 5.909 -5.591 -28.313 1.00 16.44 c c
ATOM 9822 CD LYS I 394 4.799 -5.101 -27.382 1.00 20.45 c c
ATOM 9823 CE LYS I 394 4.989 -5.604 -25.955 1.00 23.05 c c
ATOM 9824 NZ LYS I 394 5.685 -4.608 -25.094 1.00 24.13 c N
ATOM 9825 C LYS I 394 9.370 -4.087 -29.239 1.00 14.00 c c ATOM 9826 O LYS 1 394 10.260 -4.760 -28.720 1.00 14.14 C O
ATOM 9827 N ILE I 395 9.497 -2.797 -29.507 1.00 13.28 C N
ATOM 9828 CA ILE I 395 10.750 -2.193 -29.919 1.00 12.89 C C
ATOM 9829 CB ILE I 395 10.960 -2.334 -31.435 1.00 12.75 C C
ATOM 9830 CGI ILE I 395 11.556 -3.695 -31.786 1.00 13.58 C C
ATOM 9831 CD1 ILE I 395 11.347 -4.084 -33.236 1.00 15.33 C C
ATOM 9832 CG2 ILE I 395 11.838 -1.216 -31.951 1.00 12.16 C C
ATOM 9833 C ILE 1 395 10.534 -0.722 -29.648 1.00 13.15 C C
ATOM 9834 O ILE 1 395 9.437 -0.210 -29.867 1.00 13.45 C O
ATOM 9835 N MET 1 396 11.597 -0.002 -29.330 1.00 13.06 C N
ATOM 9836 CA MET 1 396 11.526 1.433 -29.454 1.00 13.00 C C
ATOM 9837 CB MET 1 396 11.421 2.114 -28.088 1.00 13.34 C C
ATOM 9838 CG MET I 396 12.738 2.594 -27.506 1.00 14.30 C C
ATOM 9839 SD MET 1 396 12.483 3.421 -25.925 1.00 18.50 C S
ATOM 9840 CE MET 1 396 11.067 2.515 -25.304 1.00 17.80 C C
ATOM 9841 C MET 1 396 12.646 2.009 -30.288 1.00 12.96 C C
ATOM 9842 O MET 1 396 13.704 1.405 -30.453 1.00 13.04 C O
ATOM 9843 N TH 1 397 12.360 3.167 -30.862 1.00 12.78 C N
ATOM 9844 CA THR 1 397 13.158 3.744 -31.917 1.00 12.51 C C
ATOM 9845 CB THR 1 397 12.261 4.048 -33.134 1.00 12.39 C C
ATOM 9846 OG1 THR I 397 12.048 2.845 -33.883 1.00 12.50 C O
ATOM 9847 CG2 THR I 397 12.895 5.107 -34.026 1.00 12.55 C C
ATOM 9848 C THR 1 397 13.633 5.062 -31.330 1.00 12.58 C C
ATOM 9849 O THR 1 397 12.815 5.911 -31.001 1.00 12.88 C O
ATOM 9850 N SER I 398 14.919 5.217 -31.088 1.00 12.55 C N
ATOM 9851 CA SER I 398 15.538 6.442 -31.506 1.00 12.76 C C
ATOM 9852 CB SER I 398 16.509 6.920 -30.432 1.00 12.52 C C
ATOM 9853 OG SER I 398 17.486 7.787 -30.978 1.00 12.72 C O
ATOM 9854 C SER 1 398 16.262 5.826 -32.632 1.00 12.99 C C
ATOM 9855 O SER 1 398 16.219 6.314 -33.761 1.00 13.13 C O
ATOM 9856 N LYS 1 399 16.463 4.540 -32.418 1.00 13.01 C N
ATOM 9857 CA LYS I 399 17.619 4.000 -32.989 1.00 13.29 C C
ATOM 9858 CB LYS I 399 17.475 4.221 -34.500 1.00 13.79 C C
ATOM 9859 CG LYS I 399 15.997 4.359 -34.942 1.00 14.34 C C
ATOM 9860 CD LYS I 399 15.854 4.556 -36.445 1.00 16.43 C C
ATOM 9861 CE LYS 1 399 15.114 3.394 -37.093 1.00 17.37 C C
ATOM 9862 NZ LYS I 399 15.524 3.199 -38.511 1.00 16.62 C N
ATOM 9863 C LYS 1 399 18.632 4.961 -32.349 1.00 13.09 C C
ATOM 9864 O LYS 1 399 19.670 5.257 -32.934 1.00 12.87 C O
ATOM 9865 N THR 1 400 18.236 5.572 -31.225 1.00 13.04 C N
ATOM 9866 CA THR 1 400 19.072 6.571 -30.513 1.00 13.38 C C
ATOM 9867 CB THR 1 400 18.218 7.723 -29.906 1.00 13.74 C C
ATOM 9868 OG1 THR 1 400 16.861 7.632 -30.365 1.00 14.38 C O
ATOM 9869 CG2 THR 1 400 18.798 9.072 -30.296 1.00 14.32 C C
ATOM 9870 C THR 1 400 19.991 5.980 -29.408 1.00 13.20 C C
ATOM 9871 O THR 1 400 19.748 4.866 -28.945 1.00 13.12 C O
ATOM 9872 N ASP 1401 20.881 6.801 -28.834 1.00 12.97 C N
ATOM 9873 CA ASP 1 401 22.197 6.333 -28.331 1.00 12.50 C C
ATOM 9874 CB ASP 1 401 23.307 7.270 -28.816 1.00 12.73 C C
ATOM 9875 CG ASP 1 401 24.212 6.623 -29.841 1.00 13.98 C C
ATOM 9876 OD1 ASP 1 401 23.677 6.029 -30.801 1.00 16.55 C O
ATOM 9877 OD2 ASP 1 401 25.430 6.903 -29.814 1.00 14.80 C O
ATOM 9878 C ASP 1401 22.414 6.066 -26.816 1.00 12.13 C C
ATOM 9879 O ASP 1401 21.541 6.376 -26.002 1.00 12.31 C O
ATOM 9880 N VAL 1 402 23.721 6.022 -26.502 1.00 11.49 C N
ATOM 9881 CA VAL 1402 24.382 5.380 -25.316 1.00 10.74 C C
ATOM 9882 CB VAL 1 402 23.454 5.112 -24.128 1.00 10.60 C C
ATOM 9883 CGI VAL 1 402 24.200 4.335 -23.060 1.00 11.26 C C
ATOM 9884 CG2 VAL 1 402 22.942 6.425 -23.556 1.00 10.99 C C
ATOM 9885 C VAL 1 402 25.452 4.251 -25.504 1.00 10.24 C C ATOM 9886 O VALI402 25.773 3.895 -26.638 1.0010.30 C o
ATOM 9887 N SE I403 25.962 3.665 -24.400 1.009.76 c N
ATOM 9888 CA SE I403 27.019 2.595 -24.456 1.009.18 c c
ATOM 9889 CB SE I403 28.324 3.145 -25.036 1.009.41 c c
ATOM 9890 OG SE I403 28.274 4.554-25.165 1.0010.82 c o
ATOM 9891 C SERI403 27.325 1.652 -23.238 1.008.51 c c
ATOM 9892 O SERI403 27.347 2.099 -22.088 1.008.30 c o
ATOM 9893 N SERI404 27.642 0.376 -23.530 1.008.35 c N
ATOM 9894 CA SERI404 28.574 -0.482 -22.733 1.008.18 c c
ATOM 9895 CB SERI404 28.123 -0.585 -21.276 1.00 8.18 c c
ATOM 9896 OG SERI404 27.698 -1.901 -20.968 1.008.83 c o
ATOM 9897 C SERI404 28.789 - ■1.907 -23.310 1.007.62 c c
ATOM 9898 O SERI404 28.422■ -2.171 -24.455 1.007.57 c o
ATOM 9899 N SERI405 29.368 ■ -2.817 -22.514 1.007.08 c N
ATOM 9900 CA SERI405 29.672 -4.192-22.973 1.006.53 c c
ATOM 9901 CB SERI405 31.139 -4.335 -23.400 1.00 6.42 c c
ATOM 9902 OG SERI405 31.467 -5.695 -23.651 1.005.66 c o
ATOM 9903 C SERI405 29.300 - -5.333 -22.012 1.006.28 c c
ATOM 9904 O SERI405 29.334■ -5.169 -20.791 1.005.98 c o
ATOM 9905 N VALI406 29.215 -6.535 -22.576 1.00 6.22 c N
ATOM 9906 CA VALI406 28.714 -7.705 -21.866 1.006.50 c c
ATOM 9907 CB VALI406 27.208 -7.894-22.099 1.00 6.45 c c
ATOM 9908 CG1VALI406 26.661 -8.972 -21.181 1.007.66 C C
ATOM 9909 CG2VALI406 26.470 -6.577 -21.903 1.007.38 C C
ATOM 9910 C VALI406 29.424 -8.942-22.388 1.006.24 C C
ATOM 9911 O VALI406 29.397 -9.228 -23.584 1.00 6.14 C O
ATOM 9912 N ILE 1407 30.041 -9.689 -21.485 1.006.32 C N
ATOM 9913 CA ILE 1407 30.831 -10.838 -21.881 1.006.60 C C
ATOM 9914 CB ILE 1407 32.035 -11.021 -20.959 1.00 6.27 C C
ATOM 9915 CGI ILE 1407 33.112 -9.989 -21.295 1.006.19 C C
ATOM 9916 CD1 ILE 1407 33.720 -9.323 -20.073 1.008.34 C C
ATOM 9917 CG2ILEI407 32.567 -12.438 -21.053 1.006.42 C C
ATOM 9918 C ILE 1407 29.995 -12.110-21.882 1.007.20 C C
ATOM 9919 O ILE 1407 29.246 -12.376-20.944 1.007.42 C O
ATOM 9920 N THR 1408 30.163 -12.914 -22.925 1.007.57 C N
ATOM 9921 CA THR 1408 29.355 -14.113 -23.103 1.008.19 C C
ATOM 9922 CB THR 1408 28.681 -14.138 -24.483 1.008.15 C C
ATOM 9923 OG1 THR 1408 29.684 -14.218 -25.503 1.008.88 C O
ATOM 9924 CG2 THR 1408 27.853 -12.888 -24.693 1.007.93 C C
ATOM 9925 C THR 1408 30.192 -15.376 -22.966 1.00 8.55 C C
ATOM 9926 O THR 1408 31.419 -15.333 -23.065 1.009.07 C O
ATOM 9927 N SERI409 29.503 -16.512 -22.970 1.00 8.70 C N
ATOM 9928 CA SER 1409 30.146 -17.813 -22.838 1.009.20 C C
ATOM 9929 CB SER 1409 29.126-18.935 -23.044 1.009.72 C C
ATOM 9930 OG SER 1409 27.946-18.700-22.297 1.0010.75 C O
ATOM 9931 C SERI409 31.268 -17.958 -23.848 1.009.01 C C
ATOM 9932 O SER 1409 32.299 -18.571 -23.567 1.009.02 C O
ATOM 9933 N LEU 1410 31.027 -17.458 -25.053 1.00 8.91 C N
ATOM 9934 CA LEU 1410 31.814 -17.858 -26.204 1.009.29 C C
ATOM 9935 CB LEU 1410 31.024 -18.828 -27.081 1.009.61 C C
ATOM 9936 CG LEU 1410 31.702 -20.180 -27.323 1.009.70 C C
ATOM 9937 CD1 LEU 1410 31.975 -20.908 -26.014 1.0011.11 C C
ATOM 9938 CD2 LEU 1410 30.895 -21.057 -28.274 1.009.16 C C
ATOM 9939 C LEU 1410 32.250-16.644-27.009 1.009.12 C C
ATOM 9940 O LEU 1410 32.844-16.774-28.077 1.009.08 C O
ATOM 9941 N GLYI411 32.016-15.462 -26.454 1.009.03 C N
ATOM 9942 CA GLYI411 32.612-14.247 -26.984 1.008.44 C C
ATOM 9943 C GLYI411 32.234 -13.047 -26.146 1.007.91 C C
ATOM 9944 O GLYI411 32.175 -13.131 -24.921 1.007.85 C O
ATOM 9945 N ALAI412 31.868 -11.961 -26.816 1.007.30 C N ATOM 9946 CA ALA 1412 31.416 -10.757 -26.130 1.006.92 C c
ATOM 9947 CB ALA I 412 32.609 -9.925 -25.672 1.00 6.90 C c
ATOM 9948 C ALA I 412 30.502 -9.934 -27.029 1.006.99 c c
ATOM 9949 O ALA I 412 30.597 -10.004 -28.255 1.006.94 c o
ATOM 9950 N ILEI413 29.567 -9.216 -26.418 1.007.29 C N
ATOM 9951 CA ILEI413 28.808 -8.200 -27.136 1.007.49 c c
ATOM 9952 CB ILEI413 27.296 -8.285 -26.846 1.007.24 c c
ATOM 9953 CGI ILEI413 26.703 -9.550 -27.480 1.007.18 c c
ATOM 9954 CD1 ILEI413 25.397 -9.315 -28.241 1.007.70 c c
ATOM 9955 CG2ILEI413 26.585 -7.051 -27.397 1.007.70 c c
ATOM 9956 C ILEI413 29.304 -6.811 -26.776 1.007.94 c c
ATOM 9957 O ILEI413 29.806 -6.591 -25.674 1.008.39 c o
ATOM 9958 N VALI414 29.155 -5.871 -27.703 1.00 8.22 c N
ATOM 9959 CA VALI414 29.498 -4.485 -27.420 1.008.77 c c
ATOM 9960 CB VALI414 30.965 -4.158 -27.782 1.00 8.57 c c
ATOM 9961 CGI VALI414 31.293 -4.627 -29.197 1.009.12 c c
ATOM 9962 CG2 VALI414 31.245 -2.669 -27.607 1.00 8.90 c c
ATOM 9963 C VALI414 28.536 -3.470 -28.028 1.008.92 c c
ATOM 9964 O VALI414 28.246 -3.497 -29.227 1.009.00 c o
ATOM 9965 N SE I415 27.947 -2.665 -27.152 1.008.97 c N
ATOM 9966 CA SE I415 27.023 -1.623 -27.552 1.009.02 c c
ATOM 9967 CB SE I415 25.805 -1.623 -26.629 1.00 8.98 c c
ATOM 9968 OG SE I415 25.203 -2.903 -26.581 1.009.54 c o
ATOM 9969 C SERI415 27.727 -0.277 -27.480 1.009.36 c c
ATOM 9970 O SERI415 27.996 0.230 -26.392 1.009.61 c o
ATOM 9971 N CYSI416 28.219 0.177 -28.626 1.009.57 c N
ATOM 9972 CA CYSI416 28.920 1.447 -28.701 1.009.61 c c
ATOM 9973 CB CYSI416 30.167 1.320 -29.572 1.009.62 c c
ATOM 9974 SG CYS 1416 31.508 2.403 -29.060 1.0011.33 c s
ATOM 9975 C CYS I 416 28.011 2.519 -29.270 1.009.61 c c
ATOM 9976 O CYS I 416 27.619 2.458 -30.434 1.009.80 c o
ATOM 9977 N TYRI417 27.662 3.493 -28.441 1.009.48 c N
ATOM 9978 CA TYRI417 26.667 4.475 -28.829 1.009.28 c c
ATOM 9979 CB TYRI417 25.305 4.117 -28.235 1.009.17 c c
ATOM 9980 CG TYRI417 24.629 2.955 -28.924 1.008.71 c c
ATOM 9981 CD1 TYRI417 23.902 2.024 -28.199 1.008.54 c c
ATOM 9982 CE1 TYRI417 23.228 0.999 -28.830 1.009.56 c c
ATOM 9983 CZ TYRI417 23.289 0.886 -30.201 1.009.83 c c
ATOM 9984 OH TYRI417 22.658 -0.162 -30.829 1.0010.51 c o
ATOM 9985 CE2TYRI417 24.025 1.783 -30.942 1.009.36 c c
ATOM 9986 CD2 TYRI417 24.675 2.818 -30.305 1.008.95 c c
ATOM 9987 C TYRI417 27.076 5.885 -28.422 1.009.35 c c
ATOM 9988 O TYRI417 28.046 6.075 -27.687 1.009.11 c o
ATOM 9989 N GLYI418 26.357 6.872 -28.946 1.009.71 c N
ATOM 9990 CA GLYI418 26.662 8.270 -28.679 1.009.95 c c
ATOM 9991 C GLYI418 28.094 8.602-29.035 1.0010.09 c c
ATOM 9992 O GLYI418 28.623 8.112 -30.033 1.0010.17 c o
ATOM 9993 N LYSI419 28.768 9.307 -28.136 1.0010.17 c N
ATOM 9994 CA LYS 1419 30.104 9.810-28.415 1.0010.50 c c
ATOM 9995 CB LYS I 419 30.381 11.077 -27.607 1.0011.09 c c
ATOM 9996 CG LYS 1419 29.942 12.351 -28.300 1.0012.94 c c
ATOM 9997 CD LYS 1419 30.697 13.553 -27.770 1.0015.52 c c
ATOM 9998 CE LYS 1419 30.546 14.735 -28.708 1.0017.07 c c
ATOM 9999 NZ LYS 1419 29.200 14.756-29.349 1.0019.30 c N
ATOM 10000 C LYS I 419 31.201 8.777 -28.168 1.0010.23 c c
ATOM 10001 O LYS 1419 32.380 9.063 -28.374 1.0010.58 c o
ATOM 10002 N THRI420 30.823 7.592 -27.697 1.0010.10 c N
ATOM 10003 CA THRI420 31.789 6.687 -27.076 1.009.74 c c
ATOM 10004 CB THRI420 31.106 5.656 -26.158 1.009.28 c c
ATOM 10005 OG1 THR I 420 29.766 6.076 -25.878 1.009.21 c : o ATOM 10006 CG2 TH I 420 31.870 5.521 -24.851 1.00 9.03 C c
ATOM 10007 C THR I 420 32.671 5.966 -28.096 1.00 9.95 c c
ATOM 10008 O THR I 420 32.289 5.800 -29.254 1.00 10.35 c o
ATOM 10009 N LYS I 421 33.880 5.608 -27.674 1.00 10.07 c N
ATOM 10010 CA LYS 1 421 34.808 4.863 -28.521 1.00 10.21 c c
ATOM 10011 CB LYS 1421 36.194 5.513 -28.495 1.00 10.30 c c
ATOM 10012 CG LYS 1 421 36.445 6.496 -29.626 1.00 12.43 c c
ATOM 10013 CD LYS 1 421 37.766 7.225 -29.441 1.00 15.12 c c
ATOM 10014 CE LYS I 421 37.752 8.578 -30.134 1.00 15.21 c c
ATOM 10015 NZ LYS 1421 38.779 9.500 -29.575 1.00 15.98 c N
ATOM 10016 C LYS I 421 34.908 3.412 -28.063 1.00 10.09 c c
ATOM 10017 O LYS 1421 34.979 3.137 -26.866 1.00 10.36 c o
ATOM 10018 N CYS I 422 34.937 2.486 -29.017 1.00 9.81 c N
ATOM 10019 CA CYS I 422 35.063 1.075 -28.681 1.00 9.56 c c
ATOM 10020 CB CYS I 422 33.696 0.396 -28.633 1.00 9.72 c c
ATOM 10021 SG CYS 1422 32.479 1.300 -27.664 1.00 11.42 c s
ATOM 10022 C CYS 1422 36.012 0.311 -29.590 1.00 9.18 c c
ATOM 10023 O CYS I 422 36.111 0.582 -30.787 1.00 9.27 c o
ATOM 10024 N THR I 423 36.636 -0.710 -29.016 1.00 8.93 c N
ATOM 10025 CA THR I 423 37.825 -1.322 -29.583 1.00 8.64 c c
ATOM 10026 CB THR I 423 39.104 -0.757 -28.940 1.00 8.32 c c
ATOM 10027 OG1 THR I 423 39.059 0.675 -28.954 1.00 7.97 c o
ATOM 10028 CG2 THR I 423 40.336 -1.230 -29.695 1.00 8.36 c c
ATOM 10029 C THR I 423 37.771 -2.810 -29.287 1.00 8.86 c c
ATOM 10030 O THR I 423 37.514 -3.214 -28.153 1.00 9.26 c o
ATOM 10031 N ALA I 424 37.993 -3.625 -30.310 1.00 8.74 c N
ATOM 10032 CA ALA I 424 38.356 -5.018 -30.097 1.00 8.79 c c
ATOM 10033 CB ALA I 424 37.512 -5.927 -30.977 1.00 8.94 c c
ATOM 10034 C ALA I 424 39.839 -5.233 -30.371 1.00 8.84 c c
ATOM 10035 O ALA I 424 40.316 -4.985 -31.477 1.00 9.24 c o
ATOM 10036 N SER I 425 40.570 - ■5.661 -29.347 1.00 8.81 c N
ATOM 10037 CA SER I 425 41.990 -5.958 -29.492 1.00 8.85 c c
ATOM 10038 CB SER I 425 42.803 -5.192 -28.446 1.00 8.94 c c
ATOM 10039 OG SER I 425 42.091 -4.060 -27.976 1.00 7.69 c o
ATOM 10040 C SER I 425 42.253 - 7.456 -29.368 1.00 9.01 c c
ATOM 10041 O SER I 425 41.541 - ■8.163 -28.656 1.00 8.63 c o
ATOM 10042 N ASN I 426 43.246 -7.944 -30.102 1.00 9.54 c N
ATOM 10043 CA ASN I 426 43.519 -9.374 -30.153 1.00 10.19 c c
ATOM 10044 CB ASN I 426 44.105 -9.764 -31.511 1.00 9.77 c c
ATOM 10045 CG ASN I 426 45.597 -9.506 -31.599 1.00 9.43 c c
ATOM 10046 OD1 ASN I 426 46.249 -9.211 -30.597 1.00 9.01 c o
ATOM 10047 ND2 ASN I 426 46.146 -9.616 -32.803 1.00 9.01 c N
ATOM 10048 C ASN I 426 44.434 -9.853 -29.029 1.00 11.16 c c
ATOM 10049 O ASN I 426 44.674 -9.138 -28.056 1.00 11.06 c o
ATOM 10050 N LYS 1427 44.921 - 11.083 -29.170 1.00 12.38 c N
ATOM 10051 CA LYS I 427 45.803 -11.703 -28.185 1.00 13.52 c c
ATOM 10052 CB LYS 1427 46.418 -12.978 -28.765 1.00 14.00 c c
ATOM 10053 CG LYS I 427 45.683 -14.255 -28.398 1.00 16.18 c c
ATOM 10054 CD LYS I 427 46.510 -15.478 -28.758 1.00 18.24 c c
ATOM 10055 CE LYS I 427 46.211 -16.641 -27.828 1.00 19.72 c c
ATOM 10056 NZ LYS 1427 46.794 -16.434 -26.474 1.00 21.43 c N
ATOM 10057 C LYS I 427 46.915 - 10.758 -27.741 1.00 13.71 c c
ATOM 10058 O LYS 1427 47.180 - 10.611 -26.547 1.00 13.63 c o
ATOM 10059 N ASN I 428 47.634 - 10.210 -28.716 1.00 14.28 c N
ATOM 10060 CA ASN I 428 48.816 -9.400 -28.447 1.00 14.60 c c
ATOM 10061 CB ASN I 428 49.709 -9.331 -29.689 1.00 14.57 c c
ATOM 10062 CG ASN I 428 49.589 -10.565 -30.563 1.00 13.24 c : c
ATOM 10063 OD1 ASN I 428 49.765 -11.690 -30.096 1.00 9.74 c o
ATOM 10064 ND2 ASN I 428 49.319 -10.358 -31.847 1.00 12.83 C N
ATOM 10065 C ASN I 428 48.466 -7.989 -27.982 1.00 14.83 c c ATOM 10066 O ASN 1 428 49.330 -7.255 -27.499 1.00 15.25 C O
ATOM 10067 N ARG 1 429 47.225 -7.580 -28.226 1.00 14.78 C N
ATOM 10068 CA ARG 1 429 46.775 -6.234 -27.885 1.00 14.74 C C
ATOM 10069 CB ARG 1 429 47.695 -5.603 -26.837 1.00 14.93 C C
ATOM 10070 CG ARG 1 429 47.475 -6.121 -25.424 1.00 16.26 C C
ATOM 10071 CD ARG 1 429 46.452 -5.279 -24.677 1.00 19.79 C C
ATOM 10072 NE ARG 1 429 45.979 -5.940 -23.464 1.00 22.68 C N
ATOM 10073 CZ ARG 1 429 46.735 -6.172 -22.396 1.00 23.54 C C
ATOM 10074 NH1 ARG I 429 48.013 -5.817 -22.394 1.00 22.87 C N
ATOM 10075 NH2 ARG I 429 46.219 -6.777 -21.335 1.00 23.53 C N
ATOM 10076 C ARG 1 429 46.689 -5.339 -29.117 1.00 14.35 C C
ATOM 10077 O ARG 1 429 46.093 -4.262 -29.073 1.00 14.62 C O
ATOM 10078 N GLY 1 430 47.270 -5.798 -30.221 1.00 13.67 C N
ATOM 10079 CA GLY 1 430 46.898 -5.304 -31.540 1.00 12.80 C C
ATOM 10080 C GLY 1 430 45.397 -5.149 -31.683 1.00 12.11 C C
ATOM 10081 O GLY 1 430 44.634 -6.038 -31.306 1.00 12.18 C O
ATOM 10082 N ILE I 431 44.972 -4.001 -32.199 1.00 11.58 C N
ATOM 10083 CA ILE I 431 43.552 -3.678 -32.300 1.00 10.76 C C
ATOM 10084 CB ILE I 431 43.321 -2.162 -32.138 1.00 10.43 C C
ATOM 10085 CGI ILE 1431 43.649 -1.718 -30.711 1.00 10.95 C C
ATOM 10086 CD1 ILE 1431 44.264 -0.337 -30.628 1.00 12.08 C C
ATOM 10087 CG2 ILE I 431 41.892 -1.796 -32.507 1.00 10.07 C C
ATOM 10088 C ILE I 431 43.011 -4.108 -33.660 1.00 10.68 C C
ATOM 10089 O ILE 1 431 43.474 -3.623 -34.693 1.00 10.40 C O
ATOM 10090 N ILE 1 432 42.063 -5.041 -33.669 1.00 10.90 C N
ATOM 10091 CA ILE I 432 41.497 -5.518 -34.931 1.00 11.42 C C
ATOM 10092 CB ILE 1 432 41.106 -7.008 -34.884 1.00 11.63 C C
ATOM 10093 CGI ILE 1432 41.784 -7.712 -33.709 1.00 12.68 C C
ATOM 10094 CD1 ILE I 432 41.172 -9.055 -33.369 1.00 13.89 C C
ATOM 10095 CG2 ILE 1432 41.453 -7.689 -36.201 1.00 12.24 C C
ATOM 10096 C ILE 1 432 40.290 -4.703 -35.381 1.00 11.41 C C
ATOM 10097 O ILE 1 432 40.172 -4.362 -36.558 1.00 11.63 C O
ATOM 10098 N LYS I 433 39.315 -4.555 -34.492 1.00 11.52 C N
ATOM 10099 CA LYS I 433 38.076 -3.878 -34.848 1.00 11.96 C C
ATOM 10100 CB LYS I 433 36.864 -4.767 -34.566 1.00 12.31 C C
ATOM 10101 CG LYS 1 433 35.552 -4.201 -35.092 1.00 14.42 C C
ATOM 10102 CD LYS 1 433 34.622 -5.301 -35.578 1.00 16.74 C C
ATOM 10103 CE LYS 1 433 33.367 -4.723 -36.216 1.00 17.08 C C
ATOM 10104 NZ LYS 1433 33.135 -5.263 -37.585 1.00 17.30 C N
ATOM 10105 C LYS 1 433 37.934 -2.543 -34.128 1.00 11.65 C C
ATOM 10106 O LYS 1433 38.620 -2.281 -33.140 1.00 11.48 C O
ATOM 10107 N THR 1 434 37.059 -1.691 -34.651 1.00 11.28 C N
ATOM 10108 CA THR 1 434 36.764 -0.407 -34.027 1.00 11.21 C C
ATOM 10109 CB THR 1 434 37.809 0.653 -34.414 1.00 11.30 C C
ATOM 10110 OG1 THR 1 434 37.324 1.955 -34.062 1.00 11.83 C O
ATOM 10111 CG2 THR 1 434 38.088 0.608 -35.910 1.00 11.84 C C
ATOM 10112 C THR 1 434 35.380 0.083 -34.446 1.00 10.94 C C
ATOM 10113 O THR 1 434 34.982 -0.085 -35.597 1.00 10.93 C O
ATOM 10114 N PHE I 435 34.604 0.572 -33.484 1.00 11.10 C N
ATOM 10115 CA PHE 1 435 33.176 0.281 -33.466 1.00 11.96 C C
ATOM 10116 CB PHE 1435 32.726 -0.248 -32.106 1.00 11.51 C C
ATOM 10117 CG PHE 1 435 32.896 -1.732 -31.957 1.00 11.19 C C
ATOM 10118 CD1 PHE I 435 33.805 -2.246 -31.047 1.00 10.86 C C
ATOM 10119 CE1 PHE I 435 34.022 -3.608 -30.957 1.00 10.24 C C
ATOM 10120 CZ PHE 1435 33.375 -4.467 -31.823 1.00 9.89 C C
ATOM 10121 CE2 PHE I 435 32.512 -3.963 -32.774 1.00 10.78 C C
ATOM 10122 CD2 PHE I 435 32.300 -2.599 -32.858 1.00 11.14 C C
ATOM 10123 C PHE 1435 32.255 1.381 -33.984 1.00 13.00 C C
ATOM 10124 O PHE 1435 32.168 2.466 -33.407 1.00 13.03 C O
ATOM 10125 N SER I 436 31.429 1.001 -34.954 1.00 13.89 C N ATOM 10126 CA SE I436 30.556 1.929 -35.657 1.0014.67 C c
ATOM 10127 CB SE I436 30.282 1.417 -37.074 1.0015.04 c c
ATOM 10128 OG SE I436 30.877 2.256 -38.049 1.0016.58 c o
ATOM 10129 C SE I436 29.240 2.105 -34.903 1.0014.75 c c
ATOM 10130 O SERI436 28.192 1.626 -35.340 1.0014.75 c o
ATOM 10131 N ASNI437 29.302 2.785 -33.764 1.0014.44 c N
ATOM 10132 CA ASNI437 28.124 3.433 -33.203 1.0014.35 c c
ATOM 10133 CB ASNI437 27.891 4.781 -33.881 1.0014.75 c c
ATOM 10134 CG ASNI437 26.889 5.641 -33.139 1.0015.51 c c
ATOM 10135 OD1 ASNI437 27.054 5.920 -31.951 1.0016.85 c o
ATOM 10136 ND2 ASN I 437 25.878 6.120 -33.856 1.0016.10 c N
ATOM 10137 C ASN I 437 26.885 2.558 -33.345 1.0013.69 c c
ATOM 10138 O ASN I 437 25.912 2.941 -33.995 1.0013.40 c o
ATOM 10139 N GLYI438 26.957 1.358 -32.782 1.0013.39 c N
ATOM 10140 CA GLYI438 25.931 0.345 -32.986 1.0012.92 c c
ATOM 10141 C GLYI438 26.000 -0.743 -31.934 1.0012.72 c c
ATOM 10142 O GLYI438 26.154 -0.459 -30.747 1.0012.83 c o
ATOM 10143 N CYSI439 25.949 -1.996 -32.375 1.0012.17 c N
ATOM 10144 CA CYS I 439 26.014 -3.126-31.456 1.0011.52 c c
ATOM 10145 CB CYS I 439 24.672 -3.321 -30.750 1.0011.68 c c
ATOM 10146 SG CYS 1439 24.046 -5.015 -30.795 1.0012.89 c s
ATOM 10147 C CYS 1439 26.437 -4.411 -32.159 1.0010.95 c c
ATOM 10148 O CYS I 439 25.714 -4.935 -33.007 1.0010.77 c o
ATOM 10149 N ASP I 440 27.617 -4.909 -31.802 1.0010.41 c N
ATOM 10150 CA ASP 1440 28.240 -6.017 -32.518 1.0010.06 c c
ATOM 10151 CB ASP I 440 29.514 -5.548 -33.224 1.0010.85 c c
ATOM 10152 CG ASP 1440 29.336 -5.417 -34.724 1.0013.11 c c
ATOM 10153 OD1 ASP I 440 29.376 -6.453 -35.422 1.0014.97 c o
ATOM 10154 OD2 ASP I 440 29.192 -4.275 -35.209 1.0015.27 c o
ATOM 10155 C ASP I 440 28.566 -7.175 -31.578 1.009.01 C 1 c
ATOM 10156 O ASP I 440 28.479 -7.040 -30.358 1.009.09 c 0
ATOM 10157 N TYRI441 29.027 -8.280 -32.159 1.007.92 c N
ATOM 10158 CA TYRI441 29.448 -9.461 -31.403 1.007.24 c c
ATOM 10159 CB TYRI441 28.448 -10.605 -31.610 1.007.04 c c
ATOM 10160 CG TYRI441 28.862 -11.916 -30.979 1.006.77 c c
ATOM 10161 CD1 TYRI441 28.439 -12.256-29.701 1.007.41 c c
ATOM 10162 CE1 TYRI441 28.805 -13.460 -29.122 1.006.79 c c
ATOM 10163 CZ TYRI441 29.529 -14.381 -29.855 1.006.49 c c
ATOM 10164 OH TYRI441 29.907 -15.573 -29.277 1.005.09 c o
ATOM 10165 CE2TYRI441 29.946 -14.076-31.134 1.007.52 c c
ATOM 10166 CD2TYRI441 29.600 -12.853 -31.694 1.007.12 c c
ATOM 10167 C TYRI441 30.833 -9.902 -31.872 1.00 6.89 c c
ATOM 10168 O TYRI441 31.150 -9.809 -33.058 1.007.12 c o
ATOM 10169 N VALI442 31.664 -10.363 -30.944 1.006.73 c N
ATOM 10170 CA VALI442 32.959 -10.941 -31.301 1.006.78 c c
ATOM 10171 CB VALI442 34.133 -10.008 -30.925 1.006.51 c c
ATOM 10172 CGI VAL I 442 34.206 -8.830 -31.879 1.007.38 c c
ATOM 10173 CG2 VAL I 442 34.007 -9.530 -29.488 1.006.00 c c
ATOM 10174 C VAL I 442 33.142 -12.285 -30.609 1.007.13 c c
ATOM 10175 O VAL I 442 32.307 -12.689 -29.800 1.007.77 c o
ATOM 10176 N SERI443 34.241 -12.970-30.908 1.007.12 c N
ATOM 10177 CA SERI443 34.476 -14.283 -30.321 1.007.64 c c
ATOM 10178 CB SERI443 33.940 -15.391 -31.233 1.007.83 c c
ATOM 10179 OG SERI443 34.994 -16.091 -31.870 1.007.99 c o
ATOM 10180 C SERI443 35.932-14.541 -29.940 1.008.16 c c
ATOM 10181 O SERI443 36.841 -13.847 -30.399 1.008.69 c o
ATOM 10182 N ASN I 444 36.135 -15.517 -29.058 1.00 8.73 c N
ATOM 10183 CA ASN I 444 37.473 -15.972 -28.692 1.009.50 c c
ATOM 10184 CB ASN I 444 37.408 -16.989 -27.546 1.009.65 c c
ATOM 10185 CG ASN I 444 36.105 -16.916 -26.772 1.0010.64 c c ATOM 10186 OD1 ASN I 444 35.530 -15.839 -26.602 1.00 12.28 C O
ATOM 10187 ND2 ASN 1 444 35.617 -18.069 -26.325 1.00 11.75 C N
ATOM 10188 C ASN 1 444 38.240 -16.558 -29.877 1.00 10.24 C C
ATOM 10189 O ASN 1 444 37.657 -17.206 -30.748 1.00 9.89 C O
ATOM 10190 N LYS 1445 39.565 -16.467 -29.809 1.00 11.63 C N
ATOM 10191 CA LYS 1 445 40.394 -16.179 -30.979 1.00 13.07 C C
ATOM 10192 CB LYS 1445 40.843 -17.470 -31.664 1.00 13.70 C C
ATOM 10193 CG LYS 1 445 41.782 -17.255 -32.848 1.00 15.80 C C
ATOM 10194 CD LYS 1 445 42.771 -16.114 -32.613 1.00 18.31 C C
ATOM 10195 CE LYS 1 445 42.855 -15.717 -31.146 1.00 19.03 C C
ATOM 10196 NZ LYS 1445 43.703 -16.652 -30.355 1.00 20.02 C N
ATOM 10197 C LYS 1 445 39.701 -15.268 -31.980 1.00 12.96 C C
ATOM 10198 O LYS 1445 38.486 -15.336 -32.159 1.00 13.24 C O
ATOM 10199 N GLY 1 446 40.491 -14.448 -32.664 1.00 13.08 C N
ATOM 10200 CA GLY 1 446 40.131 -13.057 -32.889 1.00 12.42 C C
ATOM 10201 C GLY I 446 40.305 -12.233 -31.631 1.00 11.83 C C
ATOM 10202 O GLY 1 446 41.402 -11.756 -31.342 1.00 12.44 C O
ATOM 10203 N VAL 1 447 39.264 -12.192 -30.808 1.00 10.63 C N
ATOM 10204 CA VAL 1 447 39.157 -11.162 -29.785 1.00 10.01 C C
ATOM 10205 CB VAL 1 447 37.758 -10.516 -29.764 1.00 9.97 C C
ATOM 10206 CGI VAL 1 447 37.778 -9.225 -28.957 1.00 10.51 C C
ATOM 10207 CG2 VAL I 447 37.287 -10.244 -31.180 1.00 10.50 C C
ATOM 10208 C VAL 1 447 39.548 -11.648 -28.390 1.00 9.53 C C
ATOM 10209 O VAL 1 447 39.184 -12.747 -27.967 1.00 9.61 C O
ATOM 10210 N ASP 1 448 40.211 -10.766 -27.652 1.00 9.16 C N
ATOM 10211 CA ASP I 448 40.803 -11.093 -26.362 1.00 8.75 C C
ATOM 10212 CB ASP 1 448 42.325 -11.159 -26.502 1.00 9.22 C C
ATOM 10213 CG ASP 1448 42.975 -12.024 -25.443 1.00 11.44 C C
ATOM 10214 OD1 ASP I 448 42.372 -12.204 -24.365 1.00 13.83 C O
ATOM 10215 OD2 ASP I 448 44.119 -12.472 -25.665 1.00 14.13 C O
ATOM 10216 C ASP 1 448 40.427 -9.976 -25.398 1.00 8.18 C C
ATOM 10217 O ASP 1 448 40.203 -10.209 -24.211 1.00 8.06 C O
ATOM 10218 N TH 1 449 40.201 -8.794 -25.964 1.00 7.63 C N
ATOM 10219 CA THR 1 449 39.894 -7.592 -25.197 1.00 6.80 C C
ATOM 10220 CB THR 1 449 41.165 -6.750 -24.940 1.00 6.89 C C
ATOM 10221 OG1 THR 1 449 41.805 -7.196 -23.738 1.00 6.16 C O
ATOM 10222 CG2 THR 1 449 40.815 -5.275 -24.804 1.00 7.55 C C
ATOM 10223 C THR 1 449 38.898 -6.751 -25.987 1.00 6.53 C C
ATOM 10224 O THR 1 449 38.949 -6.708 -27.216 1.00 6.59 C O
ATOM 10225 N VAL 1 450 37.947 -6.147 -25.288 1.00 6.07 C N
ATOM 10226 CA VAL 1 450 37.318 -4.934 -25.781 1.00 6.02 C C
ATOM 10227 CB VAL 1 450 35.839 -5.158 -26.121 1.00 5.61 C C
ATOM 10228 CGI VAL I 450 35.697 -6.278 -27.136 1.00 5.32 C C
ATOM 10229 CG2 VAL 1 450 35.047 -5.460 -24.860 1.00 5.55 C C
ATOM 10230 C VAL 1 450 37.427 -3.837 -24.743 1.00 6.37 C C
ATOM 10231 O VAL 1 450 37.359 -4.097 -23.542 1.00 6.54 C O
ATOM 10232 N SER I 451 37.704 -2.626 -25.207 1.00 6.41 C N
ATOM 10233 CA SER 1451 37.571 -1.451 -24.366 1.00 6.70 C C
ATOM 10234 CB SER 1 451 38.845 -0.607 -24.422 1.00 7.13 C C
ATOM 10235 OG SER 1 451 39.573 -0.864 -25.610 1.00 9.26 C O
ATOM 10236 C SER 1 451 36.373 -0.626 -24.802 1.00 6.47 C C
ATOM 10237 O SER 1 451 36.100 -0.493 -25.994 1.00 6.54 C O
ATOM 10238 N VAL 1 452 35.577 -0.203 -23.830 1.00 6.56 C N
ATOM 10239 CA VAL 1 452 34.627 0.872 -24.050 1.00 6.31 C C
ATOM 10240 CB VAL 1 452 33.205 0.448 -23.647 1.00 5.74 C C
ATOM 10241 CGI VAL 1 452 32.189 1.471 -24.130 1.00 5.06 C C
ATOM 10242 CG2 VAL 1 452 32.891 -0.929 -24.212 1.00 5.56 C C
ATOM 10243 C VAL 1 452 35.056 2.087 -23.242 1.00 6.60 C C
ATOM 10244 O VAL 1 452 35.499 1.950 -22.102 1.00 7.04 C O
ATOM 10245 N GLY 1 453 35.141 3.234 -23.907 1.00 6.54 C N ATOM 10246 CA GLY I 453 35.790 4.395 -23.314 1.00 6.43 C c
ATOM 10247 C GLY I 453 37.010 3.964 -22.525 1.00 6.09 c c
ATOM 10248 O GLY I 453 37.910 3.328 -23.071 1.00 5.90 c o
ATOM 10249 N ASN I 454 36.985 4.188 -21.216 1.00 6.02 c N
ATOM 10250 CA ASN I 454 38.156 3.904 -20.396 1.00 6.39 c c
ATOM 10251 CB ASN I 454 38.491 5.088 -19.491 1.00 6.81 c c
ATOM 10252 CG ASN I 454 39.518 6.009 -20.108 1.00 8.99 c c
ATOM 10253 OD1 ASN I 454 40.718 5.817 -19.912 1.00 11.67 c o
ATOM 10254 ND2 ASN I 454 39.073 6.836 -21.048 1.00 10.25 c N
ATOM 10255 C ASN I 454 38.053 2.617 -19.588 1.00 6.15 c c
ATOM 10256 O ASN I 454 39.041 2.154 -19.016 1.00 6.47 c o
ATOM 10257 N TH I 455 36.888 1.983 -19.635 1.00 5.40 c N
ATOM 10258 CA TH I 455 36.730 0.659 -19.057 1.00 4.53 c c
ATOM 10259 CB TH I 455 35.251 0.352 -18.737 1.00 4.70 c c
ATOM 10260 OG1 THR I 455 34.662 1.471 -18.063 1.00 5.28 c o
ATOM 10261 CG2 THR I 455 35.141 -0.878 -17.845 1.00 5.57 c c
ATOM 10262 C THR I 455 37.296 -0.399 -19.999 1.00 4.01 c c
ATOM 10263 O THR I 455 37.333 -0.204 -21.216 1.00 3.78 c o
ATOM 10264 N LEU I 456 37.885 -1.438 -19.414 1.00 3.87 c N
ATOM 10265 CA LEU I 456 38.439 -2.542 -20.189 1.00 4.05 c c
ATOM 10266 CB LEU I 456 39.946 -2.660 -19.955 1.00 3.95 c c
ATOM 10267 CG LEU I 456 40.690 -3.636 -20.868 1.00 3.76 c c
ATOM 10268 CD1 LEU I 456 40.594 -3.192 -22.319 1.00 5.35 c c
ATOM 10269 CD2 LEU 1456 42.142 -3.770 -20.440 1.00 4.10 c c
ATOM 10270 C LEU 1456 37.755 -3.858 -19.845 1.00 4.47 c c
ATOM 10271 O LEU I 456 37.769 -4.293 -18.694 1.00 4.94 c o
ATOM 10272 N TYR I 457 37.248 -4.534 -20.869 1.00 4.59 c N
ATOM 10273 CA TYR I 457 36.626 -5.839 -20.695 1.00 4.60 c c
ATOM 10274 CB TYR I 457 35.248 -5.861 -21.363 1.00 4.71 c c
ATOM 10275 CG TYR I 457 34.244 -4.912 -20.739 1.00 5.62 c c
ATOM 10276 CD1 TYR I 457 34.230 -3.563 -21.074 1.00 7.09 c c
ATOM 10277 CE1 TYR I 457 33.316 -2.697 -20.510 1.00 8.22 c c
ATOM 10278 CZ TYR I 457 32.408 -3.173 -19.588 1.00 8.06 c c
ATOM 10279 OH TYR I 457 31.469 -2.318 -19.059 1.00 8.80 c o
ATOM 10280 CE2 TYR I 457 32.381 -4.513 -19.262 1.00 7.18 c c
ATOM 10281 CD2 TYR I 457 33.302 -5.371 -19.827 1.00 6.66 c c
ATOM 10282 C TYR I 457 37.513 -6.932 -21.285 1.00 4.46 c c
ATOM 10283 O TYR I 457 38.049 -6.780 -22.383 1.00 4.92 c o
ATOM 10284 N TYR I 458 37.706 -8.009 -20.529 1.00 3.90 c N
ATOM 10285 CA TYR I 458 38.520 -9.138 -20.980 1.00 3.26 c c
ATOM 10286 CB TYR I 458 39.407 -9.632 -19.832 1.00 3.16 c c
ATOM 10287 CG TYR I 458 40.399 -8.610 -19.320 1.00 3.29 c c
ATOM 10288 CD1 TYR I 458 40.076 -7.762 -18.269 1.00 3.93 c c
ATOM 10289 CE1 TYR I 458 40.993 -6.848 -17.782 1.00 4.90 c c
ATOM 10290 CZ TYR I 458 42.245 -6.766 -18.354 1.00 5.12 c c
ATOM 10291 OH TYR I 458 43.156 -5.850 -17.881 1.00 5.42 c o
ATOM 10292 CE2 TYR I 458 42.590 -7.599 -19.395 1.00 4.72 c c
ATOM 10293 CD2 TYR I 458 41.677 -8.528 -19.858 1.00 3.89 c c
ATOM 10294 C TYR I 458 37.638 -10.293 -21.464 1.00 3.04 c c
ATOM 10295 O TYR I 458 36.897 -10.869 -20.672 1.00 3.37 c o
ATOM 10296 N VAL I 459 37.857 -10.755 -22.696 1.00 2.71 c N
ATOM 10297 CA VAL I 459 36.818 -11.487 -23.441 1.00 2.61 c c
ATOM 10298 CB VAL I 459 36.856 -11.172 -24.940 1.00 2.22 c c
ATOM 10299 CGI VAL I 459 35.936 -12.119 -25.698 1.00 2.62 c c
ATOM 10300 CG2 VAL I 459 36.459 -9.728 -25.187 1.00 2.61 c c
ATOM 10301 C VAL I 459 36.847 -13.006 -23.279 1.00 3.03 c c
ATOM 10302 O VAL I 459 37.324 -13.520 -22.267 1.00 3.21 c o
ATOM 10303 N ASN I 460 36.301 -13.724 -24.263 1.00106.93 c N
ATOM 10304 CA ASN I 460 36.733 -15.100 -24.460 1.00 95.54 c : c
ATOM 10305 CB ASN I 460 37.469 -15.533 -23.198 1.00 20.00 c c ATOM 10306 CG ASN I 460 38.132 -16.862 -23.352 1.00 20.00 C c
ATOM 10307 OD1 ASN I 460 38.781 -17.118 -24.365 1.00 20.00 c o
ATOM 10308 ND2 ASN I 460 37.824 -17.783 -22.448 1.00 20.00 c N
ATOM 10309 C ASN I 460 35.684 -16.173 -24.797 1.00 99.41 c c
ATOM 10310 O ASN I 460 35.555 -17.141 -24.047 1.00108.91 c o
ATOM 10311 N LYS I 461 35.174 -16.182 -26.023 1.00 97.04 c N
ATOM 10312 CA LYS 1 461 34.426 -17.350 -26.495 1.00105.93 c c
ATOM 10313 CB LYS 1461 33.128 -17.516 -25.700 1.00 20.00 c c
ATOM 10314 CG LYS 1 461 33.324 -18.050 -24.284 1.00 20.00 c c
ATOM 10315 CD LYS 1 461 32.012 -18.071 -23.510 1.00 20.00 c c
ATOM 10316 CE LYS I 461 32.154 -18.798 -22.179 1.00 20.00 c c
ATOM 10317 NZ LYS 1461 30.869 -19.408 -21.736 1.00 20.00 c N
ATOM 10318 C LYS I 461 34.141 -17.231 -27.987 1.00102.28 c c
ATOM 10319 O LYS 1461 34.601 -16.289 -28.627 1.00105.02 c o
ATOM 10320 N GLN I 462 33.377 -18.164 -28.545 1.00 96.68 c N
ATOM 10321 CA GLN I 462 32.944 -18.040 -29.939 1.00105.71 c c
ATOM 10322 CB GLN I 462 33.693 -19.032 -30.836 1.00 20.00 c c
ATOM 10323 CG GLN I 462 35.184 -18.748 -30.976 1.00 20.00 c c
ATOM 10324 CD GLN I 462 35.922 -19.829 -31.741 1.00 20.00 c c
ATOM 10325 OE1 GLN I 462 35.456 -20.965 -31.841 1.00 20.00 c o
ATOM 10326 NE2 GLN I 462 37.071 -19.475 -32.303 1.00 20.00 c N
ATOM 10327 C GLN I 462 31.440 -18.235 -30.082 1.00101.50 c c
ATOM 10328 O GLN I 462 30.881 -19.193 -29.553 1.00105.94 c o
ATOM 10329 N GLU I 463 30.787 -17.335 -30.809 1.00 98.92 c N
ATOM 10330 CA GLU I 463 29.339 -17.413 -30.975 1.00108.59 c c
ATOM 10331 CB GLU I 463 28.684 -16.055 -30.712 1.00 20.00 c c
ATOM 10332 CG GLU I 463 28.617 -15.668 -29.238 1.00 20.00 c c
ATOM 10333 CD GLU I 463 28.032 -14.283 -29.019 1.00 20.00 c c
ATOM 10334 OE1 GLU I 463 27.535 -13.682 -29.995 1.00 20.00 c o
ATOM 10335 OE2 GLU I 463 27.975 -13.842 -27.851 1.00 20.00 c o
ATOM 10336 C GLU I 463 28.950 -17.934 -32.353 1.00116.39 c c
ATOM 10337 O GLU I 463 29.396 -17.411 -33.375 1.00118.70 c o
ATOM 10338 N GLY I 464 28.103 -18.957 -32.372 1.00127.70 c N
ATOM 10339 CA GLY I 464 27.598 -19.512 -33.621 1.00143.17 c c
ATOM 10340 C GLY I 464 26.466 -18.687 -34.200 1.00149.77 c c
ATOM 10341 O GLY I 464 25.945 -17.784 -33.545 1.00155.06 c o
ATOM 10342 N LYS 1465 26.088 -18.997 -35.435 1.00153.73 c N
ATOM 10343 CA LYS I 465 25.034 -18.261 -36.124 1.00153.69 c c
ATOM 10344 CB LYS 1465 23.750 -18.259 -35.293 1.00 20.00 c c
ATOM 10345 CG LYS I 465 23.099 -19.626 -35.151 1.00 20.00 c c
ATOM 10346 CD LYS I 465 21.848 -19.555 -34.292 1.00 20.00 c c
ATOM 10347 CE LYS I 465 21.188 -20.919 -34.164 1.00 20.00 c c
ATOM 10348 NZ LYS 1465 19.972 -20.869 -33.307 1.00 20.00 c N
ATOM 10349 C LYS I 465 25.466 -16.831 -36.426 1.00155.37 c c
ATOM 10350 O LYS 1465 25.158 -16.292 -37.489 1.00155.20 c o
ATOM 10351 N GLU I 472 20.477 -14.304 -43.583 1.00145.47 c N
ATOM 10352 CA GLU I 472 19.435 -13.563 -44.284 1.00151.12 c c
ATOM 10353 CB GLU I 472 18.367 -14.521 -44.821 1.00 20.00 c c
ATOM 10354 CG GLU I 472 18.856 -15.453 -45.922 1.00 20.00 c c
ATOM 10355 CD GLU I 472 17.778 -16.409 -46.402 1.00 20.00 c c
ATOM 10356 OE1 GLU I 472 16.723 -16.504 -45.739 1.00 20.00 c o
ATOM 10357 OE2 GLU I 472 17.996 -17.083 -47.430 1.00 20.00 c o
ATOM 10358 C GLU I 472 18.796 -12.521 -43.369 1.00153.35 c c
ATOM 10359 O GLU I 472 18.205 -12.866 -42.345 1.00159.41 c o
ATOM 10360 N PRO I 473 18.943 -11.236 -43.722 1.00150.51 c N
ATOM 10361 CA PRO I 473 18.346 -10.158 -42.958 1.00141.97 c c
ATOM 10362 CB PRO I 473 19.542 -9.243 -42.691 1.00 20.00 c c
ATOM 10363 CG PRO I 473 20.496 -9.502 -43.863 1.00 20.00 c c
ATOM 10364 CD PRO I 473 20.007 -10.730 -44.602 1.00 20.00 c c
ATOM 10365 C PRO 1473 17.331 -9.429 -43.824 1.00135.14 c c ATOM 10366 O PRO I 473 17.408 -9.503 -45.051 1.00144.93 c o
ATOM 10367 N ILE I 474 16.371 -8.757 -43.197 1.00118.07 c N
ATOM 10368 CA ILE I 474 15.320 -8.071 -43.939 1.00105.14 c c
ATOM 10369 CB ILE I 474 14.440 -9.067 -44.737 1.00 20.00 c c
ATOM 10370 CGI ILE 1474 15.255 -9.730 -45.856 1.00 20.00 c c
ATOM 10371 CD1 ILE 1474 14.525 -10.842 -46.588 1.00 20.00 c c
ATOM 10372 CG2 ILE 1474 13.224 -8.354 -45.317 1.00 20.00 c c
ATOM 10373 C ILE I 474 14.436 -7.226 -43.022 1.00104.75 c c
ATOM 10374 O ILE I 474 13.471 -7.725 -42.443 1.00111.83 c o
ATOM 10375 N ILE I 475 14.746 -5.934 -42.932 1.00 94.65 c N
ATOM 10376 CA ILE 1475 14.105 -5.051 -41.957 1.00 79.88 c c
ATOM 10377 CB ILE I 475 15.105 -4.568 -40.885 1.00 20.00 c c
ATOM 10378 CGI ILE 1475 15.576 -5.737 -40.014 1.00 20.00 c c
ATOM 10379 CD1 ILE 1475 16.791 -5.417 -39.163 1.00 20.00 c c
ATOM 10380 CG2 ILE 1475 14.493 -3.458 -40.043 1.00 20.00 c c
ATOM 10381 C ILE I 475 13.459 -3.835 -42.617 1.00 79.52 c c
ATOM 10382 O ILE I 475 14.150 -2.913 -43.054 1.00 82.70 c o
ATOM 10383 N ASN I 476 12.133 -3.791 -42.590 1.00 69.64 c N
ATOM 10384 CA ASN I 476 11.404 -2.621 -43.048 1.00 68.88 c c
ATOM 10385 CB ASN I 476 9.979 -3.002 -43.442 1.00 20.00 c c
ATOM 10386 CG ASN I 476 9.939 -3.881 -44.672 1.00 20.00 c c
ATOM 10387 OD1 ASN I 476 10.854 -3.856 -45.496 1.00 20.00 c o
ATOM 10388 ND2 ASN I 476 8.918 -4.722 -44.762 1.00 20.00 c N
ATOM 10389 C ASN I 476 11.401 -1.512 -42.004 1.00 67.13 c c
ATOM 10390 O ASN I 476 11.491 -1.781 -40.806 1.00 73.10 c o
ATOM 10391 N PHE I 477 11.492 -0.273 -42.474 1.00 64.95 c N
ATOM 10392 CA PHE I 477 11.535 0.883 -41.585 1.00 68.13 c c
ATOM 10393 CB PHE I 477 12.064 2.118 -42.327 1.00 20.00 c c
ATOM 10394 CG PHE I 477 13.494 1.995 -42.778 1.00 20.00 c c
ATOM 10395 CD1 PHE I 477 14.532 2.409 -41.955 1.00 20.00 c c
ATOM 10396 CE1 PHE I 477 15.842 2.359 -42.391 1.00 20.00 c c
ATOM 10397 CZ PHE 1477 16.127 1.910 -43.665 1.00 20.00 c c
ATOM 10398 CE2 PHE I 477 15.100 1.529 -44.506 1.00 20.00 c c
ATOM 10399 CD2 PHE I 477 13.791 1.596 -44.070 1.00 20.00 c c
ATOM 10400 C PHE 1477 10.167 1.186 -40.968 1.00 65.57 c c
ATOM 10401 O PHE 1477 10.033 2.109 -40.165 1.00 49.83 c o
ATOM 10402 N TY I 478 9.136 0.485 -41.432 1.00 51.97 c N
ATOM 10403 CA TYR I 478 7.811 0.580 -40.824 1.00 52.01 c c
ATOM 10404 CB TYR I 478 6.729 0.140 -41.815 1.00 20.00 c c
ATOM 10405 CG TYR I 478 6.638 1.012 -43.045 1.00 20.00 c c
ATOM 10406 CD1 TYR I 478 5.883 2.179 -43.040 1.00 20.00 c c
ATOM 10407 CE1 TYR I 478 5.824 2.997 -44.155 1.00 20.00 c c
ATOM 10408 CZ TYR I 478 6.512 2.642 -45.300 1.00 20.00 c c
ATOM 10409 OH TYR I 478 6.454 3.447 -46.414 1.00 20.00 c o
ATOM 10410 CE2 TYR I 478 7.260 1.484 -45.333 1.00 20.00 c c
ATOM 10411 CD2 TYR I 478 7.319 0.677 -44.210 1.00 20.00 c c
ATOM 10412 C TYR I 478 7.745 -0.269 -39.556 1.00 66.63 c c
ATOM 10413 O TYR I 478 6.674 -0.470 -38.983 1.00 63.45 c o
ATOM 10414 N ASP I 479 8.898 -0.790 -39.146 1.00 65.34 c N
ATOM 10415 CA ASP 1479 9.013 -1.509 -37.886 1.00 65.32 c c
ATOM 10416 CB ASP I 479 9.879 -2.758 -38.061 1.00 20.00 c c
ATOM 10417 CG ASP 1479 9.210 -3.815 -38.916 1.00 20.00 c c
ATOM 10418 OD1 ASP I 479 7.967 -3.791 -39.028 1.00 20.00 c o
ATOM 10419 OD2 ASP I 479 9.920 -4.701 -39.436 1.00 20.00 c o
ATOM 10420 C ASP I 479 9.590 -0.614 -36.796 1.00 64.83 c c
ATOM 10421 O ASP I 479 9.572 -0.976 -35.620 1.00 60.42 c o
ATOM 10422 N PRO I 480 10.076 0.579 -37.181 1.00 47.60 c N
ATOM 10423 CA PRO I 480 10.722 1.488 -36.253 1.00 46.52 c c
ATOM 10424 CB PRO I 480 11.789 2.143 -37.124 1.00 20.00 c c
ATOM 10425 CG PRO I 480 11.140 2.219 -38.487 1.00 20.00 c c ATOM 10426 CD PRO I 480 10.043 1.155 -38.536 1.00 20.00 c c
ATOM 10427 C PRO 1480 9.736 2.550 -35.806 1.00 52.36 c c
ATOM 10428 O PRO I 480 9.629 3.601 -36.438 1.00 64.15 c o
ATOM 10429 N LEU I 481 8.945 2.229 -34.792 1.00 62.90 c N
ATOM 10430 CA LEU I 481 8.005 3.187 -34.233 1.00 54.24 c c
ATOM 10431 CB LEU I 481 6.576 2.656 -34.340 1.00 20.00 c c
ATOM 10432 CG LEU I 481 6.056 2.404 -35.756 1.00 20.00 c c
ATOM 10433 CD1 LEU I 481 4.735 1.662 -35.704 1.00 20.00 c c
ATOM 10434 CD2 LEU I 481 5.911 3.711 -36.524 1.00 20.00 c c
ATOM 10435 C LEU 1481 8.346 3.496 -32.783 1.00 59.81 c c
ATOM 10436 O LEU I 481 9.346 3.015 -32.250 1.00 64.98 c o
ATOM 10437 N VAL I 482 7.562 4.375 -32.176 1.00 59.66 c N
ATOM 10438 CA VAL I 482 7.706 4.645 -30.761 1.00 49.67 c c
ATOM 10439 CB VAL I 482 7.767 6.146 -30.484 1.00 20.00 c c
ATOM 10440 CGI VAL I 482 8.060 6.388 -29.015 1.00 20.00 c c
ATOM 10441 CG2 VAL I 482 8.826 6.795 -31.358 1.00 20.00 c c
ATOM 10442 C VAL I 482 6.550 4.037 -29.987 1.00 53.03 c c
ATOM 10443 O VAL I 482 5.423 3.998 -30.476 1.00 46.27 c o
ATOM 10444 N PHE I 483 6.864 3.441 -28.842 1.00 61.61 c N
ATOM 10445 CA PHE I 483 5.847 2.831 -27.994 1.00 65.03 c c
ATOM 10446 CB PHE I 483 6.218 1.380 -27.662 1.00 20.00 c c
ATOM 10447 CG PHE I 483 6.212 0.463 -28.857 1.00 20.00 c c
ATOM 10448 CD1 PHE I 483 5.036 -0.124 -29.292 1.00 20.00 c c
ATOM 10449 CE1 PHE I 483 5.028 -0.963 -30.390 1.00 20.00 c c
ATOM 10450 CZ PHE 1483 6.201 -1.222 -31.068 1.00 20.00 c c
ATOM 10451 CE2 PHE I 483 7.379 -0.653 -30.639 1.00 20.00 c c
ATOM 10452 CD2 PHE I 483 7.382 0.185 -29.540 1.00 20.00 c c
ATOM 10453 C PHE 1483 5.627 3.653 -26.723 1.00 71.00 c c
ATOM 10454 O PHE 1483 5.934 3.199 -25.620 1.00100.44 c o
ATOM 10455 N PRO I 484 5.255 4.928 -26.903 1.00 54.44 c N
ATOM 10456 CA PRO I 484 5.000 5.815 -25.781 1.00 47.46 c c
ATOM 10457 CB PRO I 484 6.136 6.828 -25.903 1.00 20.00 c c
ATOM 10458 CG PRO I 484 6.468 6.851 -27.406 1.00 20.00 c c
ATOM 10459 CD PRO I 484 5.760 5.686 -28.058 1.00 20.00 c c
ATOM 10460 C PRO 1484 3.661 6.533 -25.944 1.00 41.56 c c
ATOM 10461 O PRO I 484 3.430 7.190 -26.959 1.00 46.53 c o
ATOM 10462 N SER I 485 2.779 6.380 -24.964 1.00 46.30 c N
ATOM 10463 CA SER I 485 1.436 6.938 -25.048 1.00 49.30 c c
ATOM 10464 CB SER I 485 0.892 7.220 -23.649 1.00 20.00 c c
ATOM 10465 OG SER I 485 1.684 8.188 -22.983 1.00 20.00 c o
ATOM 10466 C SER I 485 1.380 8.204 -25.901 1.00 41.24 c c
ATOM 10467 O SER I 485 0.643 8.262 -26.883 1.00 46.93 c o
ATOM 10468 N ASP I 486 2.103 9.238 -25.482 1.00 49.48 c N
ATOM 10469 CA ASP 1486 2.085 10.518 -26.185 1.00 37.44 c c
ATOM 10470 CB ASP I 486 3.029 11.514 -25.511 1.00 20.00 c c
ATOM 10471 CG ASP 1486 2.509 11.993 -24.173 1.00 20.00 c c
ATOM 10472 OD1 ASP I 486 1.314 11.773 -23.887 1.00 20.00 c o
ATOM 10473 OD2 ASP I 486 3.299 12.566 -23.395 1.00 20.00 c o
ATOM 10474 C ASP I 486 2.456 10.359 -27.656 1.00 45.66 c c
ATOM 10475 O ASP I 486 1.752 10.848 -28.539 1.00 39.86 c o
ATOM 10476 N GLU I 487 3.559 9.665 -27.914 1.00 49.20 C N
ATOM 10477 CA GLU I 487 4.006 9.422 -29.280 1.00 45.70 c c
ATOM 10478 CB GLU I 487 5.346 8.684 -29.288 1.00 20.00 c c
ATOM 10479 CG GLU I 487 6.491 9.481 -28.685 1.00 20.00 c c
ATOM 10480 CD GLU I 487 7.766 8.669 -28.551 1.00 20.00 c c
ATOM 10481 OE1 GLU I 487 7.722 7.447 -28.804 1.00 20.00 c o
ATOM 10482 OE2 GLU I 487 8.794 9.238 -28.122 1.00 20.00 c o
ATOM 10483 C GLU I 487 2.966 8.648 -30.085 1.00 41.48 c c
ATOM 10484 O GLU I 487 2.656 9.011 -31.219 1.00 48.92 c o
ATOM 10485 N PHE 1488 2.402 7.606 -29.483 1.00 42.16 C N ATOM 10486 CA PHE I 488 1.397 6.789 -30.155 1.00 39.33 C c
ATOM 10487 CB PHE I 488 0.968 5.623 -29.268 1.00 20.00 C c
ATOM 10488 CG PHE I 488 2.059 4.633 -29.005 1.00 20.00 c c
ATOM 10489 CD1 PHE I 488 2.403 3.694 -29.958 1.00 20.00 c c
ATOM 10490 CE1 PHE I 488 3.409 2.779 -29.715 1.00 20.00 c c
ATOM 10491 CZ PHE 1488 4.089 2.807 -28.517 1.00 20.00 c c
ATOM 10492 CE2 PHE I 488 3.752 3.737 -27.560 1.00 20.00 c c
ATOM 10493 CD2 PHE I 488 2.752 4.652 -27.810 1.00 20.00 c c
ATOM 10494 C PHE 1488 0.182 7.618 -30.540 1.00 43.06 c c
ATOM 10495 O PHE 1488 -0.328 7.508 -31.654 1.00 61.71 c o
ATOM 10496 N ASP I 489 -0.261 8.471 -29.624 1.00 41.95 c N
ATOM 10497 CA ASP 1489 -1.454 9.273 -29.851 1.00 42.75 c c
ATOM 10498 CB ASP I 489 -1.837 10.023 -28.581 1.00 20.00 c c
ATOM 10499 CG ASP 1489 -2.352 9.102 -27.504 1.00 20.00 c c
ATOM 10500 OD1 ASP I 489 -2.808 7.989 -27.848 1.00 20.00 c o
ATOM 10501 OD2 ASP I 489 -2.184 9.435 -26.313 1.00 20.00 c o
ATOM 10502 C ASP I 489 -1.255 10.256 -30.994 1.00 45.61 c c
ATOM 10503 O ASP I 489 -2.206 10.617 -31.689 1.00 54.39 c o
ATOM 10504 N ALA I 490 -0.020 10.714 -31.160 1.00 42.89 c N
ATOM 10505 CA ALA I 490 0.306 11.663 -32.215 1.00 38.40 c c
ATOM 10506 CB ALA I 490 1.684 12.262 -31.976 1.00 20.00 c c
ATOM 10507 C ALA I 490 0.240 10.994 -33.585 1.00 39.67 c c
ATOM 10508 O ALA I 490 -0.356 11.529 -34.521 1.00 56.80 c o
ATOM 10509 N SE I 491 0.803 9.793 -33.676 1.00 40.38 c N
ATOM 10510 CA SE I 491 0.721 8.992 -34.893 1.00 41.77 c c
ATOM 10511 CB SE I 491 1.611 7.752 -34.784 1.00 20.00 c c
ATOM 10512 OG SE I 491 1.132 6.864 -33.788 1.00 20.00 c o
ATOM 10513 C SER I 491 -0.717 8.580 -35.187 1.00 39.01 c c
ATOM 10514 O SER I 491 -1.142 8.563 -36.342 1.00 36.91 c o
ATOM 10515 N ILE I 492 -1.474 8.286 -34.135 1.00 38.11 C N
ATOM 10516 CA ILE I 492 -2.896 8.000 -34.280 1.00 41.21 c c
ATOM 10517 CB ILE I 492 -3.539 7.629 -32.938 1.00 20.00 c c
ATOM 10518 CGI ILE 1492 -2.964 6.311 -32.424 1.00 20.00 c c
ATOM 10519 CD1 ILE 1492 -3.501 5.906 -31.076 1.00 20.00 c c
ATOM 10520 CG2 ILE 1492 -5.050 7.533 -33.080 1.00 20.00 c c
ATOM 10521 C ILE I 492 -3.646 9.182 -34.883 1.00 39.22 c c
ATOM 10522 O ILE I 492 -4.494 9.008 -35.758 1.00 47.54 c o
ATOM 10523 N SER I 493 -3.334 10.383 -34.408 1.00 41.64 c N
ATOM 10524 CA SER I 493 -3.929 11.598 -34.952 1.00 35.15 c c
ATOM 10525 CB SER I 493 -3.483 12.820 -34.146 1.00 20.00 c c
ATOM 10526 OG SER I 493 -2.100 13.070 -34.322 1.00 20.00 c o
ATOM 10527 C SER I 493 -3.547 11.773 -36.416 1.00 47.90 c c
ATOM 10528 O SER I 493 -4.380 12.128 -37.250 1.00 50.94 c o
ATOM 10529 N GLN I 494 -2.296 11.457 -36.727 1.00 42.51 c N
ATOM 10530 CA GLN I 494 -1.784 11.587 -38.081 1.00 41.96 c c
ATOM 10531 CB GLN I 494 -0.263 11.405 -38.085 1.00 20.00 c c
ATOM 10532 CG GLN I 494 0.495 12.482 -37.308 1.00 20.00 c c
ATOM 10533 CD GLN I 494 1.989 12.210 -37.223 1.00 20.00 c c
ATOM 10534 OE1 GLN I 494 2.410 11.104 -36.881 1.00 20.00 c o
ATOM 10535 NE2 GLN I 494 2.790 13.248 -37.433 1.00 20.00 c N
ATOM 10536 C GLN I 494 -2.449 10.583 -39.023 1.00 33.86 c c
ATOM 10537 O GLN I 494 -2.944 10.950 -40.090 1.00 54.89 c o
ATOM 10538 N VAL I 495 -2.511 9.328 -38.594 1.00 34.99 c N
ATOM 10539 CA VAL I 495 -3.226 8.300 -39.341 1.00 38.42 c c
ATOM 10540 CB VAL I 495 -3.245 6.968 -38.576 1.00 20.00 c c
ATOM 10541 CGI VAL I 495 -4.032 5.922 -39.349 1.00 20.00 c c
ATOM 10542 CG2 VAL I 495 -1.828 6.497 -38.309 1.00 20.00 c c
ATOM 10543 C VAL I 495 -4.661 8.731 -39.618 1.00 42.74 c c
ATOM 10544 O VAL I 495 -5.144 8.634 -40.747 1.00 44.00 c o
ATOM 10545 N ASN I 496 -5.314 9.268 -38.592 1.00 42.45 c N ATOM 10546 CA ASN I 496 -6.705 9.685 -38.697 1.00 43.01 C c
ATOM 10547 CB ASN I 496 -7.232 10.134 -37.333 1.00 20.00 c c
ATOM 10548 CG ASN I 496 -7.416 8.977 -36.374 1.00 20.00 c c
ATOM 10549 OD1 ASN I 496 -7.439 7.817 -36.784 1.00 20.00 c o
ATOM 10550 ND2 ASN I 496 -7.495 9.283 -35.083 1.00 20.00 c N
ATOM 10551 C ASN I 496 -6.906 10.790 -39.727 1.00 43.13 c c
ATOM 10552 O ASN I 496 -7.893 10.793 -40.462 1.00 54.76 c o
ATOM 10553 N GLU I 497 -5.990 11.752 -39.744 1.00 42.08 c N
ATOM 10554 CA GLU I 497 -6.038 12.828 -40.726 1.00 43.13 c c
ATOM 10555 CB GLU I 497 -4.947 13.863 -40.443 1.00 20.00 c c
ATOM 10556 CG GLU I 497 -5.172 14.672 -39.175 1.00 20.00 c c
ATOM 10557 CD GLU I 497 -4.045 15.647 -38.896 1.00 20.00 c c
ATOM 10558 OE1 GLU I 497 -3.007 15.574 -39.587 1.00 20.00 c o
ATOM 10559 OE2 GLU I 497 -4.192 16.480 -37.977 1.00 20.00 c o
ATOM 10560 C GLU I 497 -5.884 12.275 -42.137 1.00 49.77 c c
ATOM 10561 O GLU I 497 -6.542 12.736 -43.071 1.00 42.88 c o
ATOM 10562 N LYS I 498 -5.051 11.249 -42.273 1.00 41.82 c N
ATOM 10563 CA LYS I 498 -4.855 10.579 -43.552 1.00 53.60 c c
ATOM 10564 CB LYS 1498 -3.676 9.609 -43.471 1.00 20.00 c c
ATOM 10565 CG LYS I 498 -2.336 10.274 -43.228 1.00 20.00 c c
ATOM 10566 CD LYS I 498 -1.193 9.356 -43.638 1.00 20.00 c c
ATOM 10567 CE LYS I 498 0.160 9.937 -43.247 1.00 20.00 c c
ATOM 10568 NZ LYS 1498 1.285 9.250 -43.942 1.00 20.00 c N
ATOM 10569 C LYS I 498 -6.109 9.830 -43.994 1.00 55.29 C c
ATOM 10570 O LYS 1498 -6.409 9.763 -45.186 1.00 61.06 c o
ATOM 10571 N ILE I 499 -6.766 9.165 -43.047 1.00 52.22 C N
ATOM 10572 CA ILE I 499 -8.038 8.500 -43.323 1.00 48.26 c c
ATOM 10573 CB ILE I 499 -8.586 7.785 -42.076 1.00 20.00 c c
ATOM 10574 CGI ILE 1499 -7.657 6.642 -41.667 1.00 20.00 c c
ATOM 10575 CD1 ILE 1499 -7.934 6.102 -40.286 1.00 20.00 c c
ATOM 10576 CG2 ILE 1499 -9.994 7.267 -42.333 1.00 20.00 c c
ATOM 10577 C ILE I 499 -9.067 9.516 -43.798 1.00 49.07 c c
ATOM 10578 O ILE I 499 -9.858 9.244 -44.701 1.00 58.45 c o
ATOM 10579 N ASN I 500 -8.961 10.726 -43.265 1.00 51.02 c N
ATOM 10580 CA ASN I 500 -9.845 11.812 -43.644 1.00 52.06 c c
ATOM 10581 CB ASN I 500 -9.741 12.940 -42.625 1.00 20.00 c c
ATOM 10582 CG ASN I 500 -10.861 13.933 -42.753 1.00 20.00 c c
ATOM 10583 OD1 ASN I 500 -11.927 13.622 -43.286 1.00 20.00 C O ATOM 10584 ND2 ASN I 500 -10.647 15.126 -42.232 1.00 20.00 C N
ATOM 10585 C ASN I 500 -9.552 12.345 -45.041 1.00 48.31 C c
ATOM 10586 O ASN I 500 -10.448 12.834 -45.729 1.00 56.89 c o
ATOM 10587 N GLN I 501 -8.283 12.300 -45.434 1.00 55.87 c N
ATOM 10588 CA GLN I 501 -7.900 12.610 -46.807 1.00 53.55 c c
ATOM 10589 CB GLN I 501 -6.384 12.797 -46.917 1.00 20.00 c c
ATOM 10590 CG GLN I 501 -5.851 13.987 -46.136 1.00 20.00 c c
ATOM 10591 CD GLN I 501 -4.338 14.093 -46.191 1.00 20.00 c c
ATOM 10592 OE1 GLN I 501 -3.648 13.146 -46.576 1.00 20.00 c o
ATOM 10593 NE2 GLN I 501 -3.814 15.247 -45.793 1.00 20.00 c N
ATOM 10594 C GLN I 501 -8.383 11.531 -47.777 1.00 45.67 c c
ATOM 10595 O GLN I 501 -8.980 11.837 -48.810 1.00 58.31 c o
ATOM 10596 N SE I 502 -8.234 10.273 -47.378 1.00 43.44 c N
ATOM 10597 CA SE I 502 -8.704 9.157 -48.189 1.00 45.40 c c
ATOM 10598 CB SE I 502 -8.367 7.830 -47.512 1.00 20.00 c c
ATOM 10599 OG SE I 502 -9.001 7.735 -46.250 1.00 20.00 c o
ATOM 10600 C SER I 502 -10.206 9.254 -48.413 1.00 55.15 c c
ATOM 10601 O SER I 502 -10.708 8.934 -49.490 1.00 52.57 c o
ATOM 10602 N LEU I 503 -10.920 9.673 -47.376 1.00 55.35 c N
ATOM 10603 CA LEU I 503 -12.366 9.798 -47.447 1.00 52.12 c c
ATOM 10604 CB LEU I 503 -12.950 10.025 -46.053 1.00 20.00 c c
ATOM 10605 CG LEU I 503 -12.783 8.856 -45.082 1.00 20.00 c c ATOM 10606 CD1 LEU 1 503 -13.061 9.290 -43.653 1.00 20.00 C C
ATOM 10607 CD2 LEU I 503 -13.685 7.704 -45.481 1.00 20.00 C C
ATOM 10608 C LEU 1 503 -12.761 10.938 -48.371 1.00 55.74 C C
ATOM 10609 O LEU 1 503 -13.782 10.869 -49.052 1.00 57.75 C O
ATOM 10610 N ALA 1 504 -11.951 11.991 -48.382 1.00 57.22 C N
ATOM 10611 CA ALA 1 504 -12.187 13.129 -49.261 1.00 59.12 C C
ATOM 10612 CB ALA 1 504 -11.333 14.315 -48.831 1.00 20.00 C C
ATOM 10613 C ALA 1 504 -11.902 12.760 -50.713 1.00 58.10 C C
ATOM 10614 O ALA 1 504 -12.656 13.119 -51.618 1.00 63.64 C O
ATOM 10615 N PHE 1 505 -10.813 12.029 -50.922 1.00 58.17 C N
ATOM 10616 CA PHE I 505 -10.485 11.505 -52.240 1.00 56.56 C C
ATOM 10617 CB PHE 1 505 -9.180 10.698 -52.186 1.00 20.00 C C
ATOM 10618 CG PHE 1 505 -7.971 11.517 -51.817 1.00 20.00 C C
ATOM 10619 CD1 PHE I 505 -7.307 12.270 -52.773 1.00 20.00 C C
ATOM 10620 CE1 PHE I 505 -6.230 13.063 -52.426 1.00 20.00 C C
ATOM 10621 CZ PHE 1 505 -5.768 13.067 -51.125 1.00 20.00 C C
ATOM 10622 CE2 PHE I 505 -6.376 12.270 -50.176 1.00 20.00 C C
ATOM 10623 CD2 PHE I 505 -7.471 11.499 -50.524 1.00 20.00 C C
ATOM 10624 C PHE 1 505 -11.625 10.637 -52.769 1.00 60.12 C C
ATOM 10625 O PHE 1 505 -12.014 10.746 -53.934 1.00 65.46 C O
ATOM 10626 N ILE 1 506 -12.214 9.844 -51.875 1.00 56.10 C N
ATOM 10627 CA ILE 1 506 -13.355 8.991 -52.213 1.00 57.32 C C
ATOM 10628 CB ILE 1 506 -13.782 8.109 -51.013 1.00 20.00 C C
ATOM 10629 CGI ILE 1 506 -12.657 7.149 -50.619 1.00 20.00 C C
ATOM 10630 CD1 ILE 1 506 -12.804 6.591 -49.222 1.00 20.00 C C
ATOM 10631 CG2 ILE I 506 -15.064 7.345 -51.330 1.00 20.00 C C
ATOM 10632 C ILE 1 506 -14.556 9.818 -52.669 1.00 67.33 C C
ATOM 10633 O ILE 1 506 -15.217 9.485 -53.652 1.00 76.99 C O
ATOM 10634 N A G 1 507 -14.855 10.878 -51.925 1.00 67.87 C N
ATOM 10635 CA ARG I 507 -15.936 11.788 -52.287 1.00 62.11 C C
ATOM 10636 CB ARG 1 507 -16.087 12.898 -51.240 1.00 20.00 C C
ATOM 10637 CG ARG I 507 -16.795 12.450 -49.963 1.00 20.00 C C
ATOM 10638 CD ARG 1 507 -16.736 13.504 -48.861 1.00 20.00 C C
ATOM 10639 NE ARG 1 507 -17.140 12.957 -47.566 1.00 20.00 C N
ATOM 10640 CZ ARG 1 507 -17.292 13.683 -46.463 1.00 20.00 C C
ATOM 10641 NH1 ARG I 507 -17.083 14.992 -46.499 1.00 20.00 C N
ATOM 10642 NH2 ARG I 507 -17.687 13.106 -45.335 1.00 20.00 C N
ATOM 10643 C ARG 1 507 -15.685 12.391 -53.659 1.00 67.30 C C
ATOM 10644 O ARG 1 507 -16.488 12.224 -54.574 1.00 67.02 C O
ATOM 10645 N LYS 1 508 -14.518 13.001 -53.823 1.00 66.83 C N
ATOM 10646 CA LYS I 508 -14.125 13.546 -55.112 1.00 68.12 C C
ATOM 10647 CB LYS 1 508 -12.693 14.086 -55.052 1.00 20.00 C C
ATOM 10648 CG LYS I 508 -12.522 15.286 -54.117 1.00 20.00 C C
ATOM 10649 CD LYS I 508 -11.072 15.750 -54.046 1.00 20.00 C C
ATOM 10650 CE LYS I 508 -10.912 16.933 -53.098 1.00 20.00 C C
ATOM 10651 NZ LYS 1 508 -9.486 17.329 -52.912 1.00 20.00 C N
ATOM 10652 C LYS 1 508 -14.275 12.499 -56.215 1.00 65.22 C C
ATOM 10653 O LYS 1 508 -15.005 12.710 -57.183 1.00 72.34 C O
ATOM 10654 N SER I 509 -13.727 11.312 -55.973 1.00 64.87 C N
ATOM 10655 CA SER 1 509 -13.783 10.230 -56.949 1.00 56.47 C C
ATOM 10656 CB SER 1 509 -13.014 9.008 -56.445 1.00 20.00 C C
ATOM 10657 OG SER 1 509 -13.561 8.528 -55.232 1.00 20.00 C O
ATOM 10658 C SER 1 509 -15.220 9.847 -57.299 1.00 56.96 C C
ATOM 10659 O SER 1 509 -15.537 9.599 -58.461 1.00 65.57 C O
ATOM 10660 N ASP 1 510 -16.077 9.760 -56.285 1.00 64.34 C N
ATOM 10661 CA ASP 1 510 -17.478 9.402 -56.500 1.00 64.83 C C
ATOM 10662 CB ASP 1 510 -18.217 9.244 -55.161 1.00 20.00 C C
ATOM 10663 CG ASP 1 510 -17.827 7.975 -54.416 1.00 20.00 C C
ATOM 10664 OD1 ASP I 510 -17.292 7.044 -55.050 1.00 20.00 C O
ATOM 10665 OD2 ASP I 510 -18.083 7.900 -53.197 1.00 20.00 C O ATOM 10666 C ASP 1 510 -18.173 10.458 -57.356 1.00 62.11 C C
ATOM 10667 O ASP 1 510 -18.723 10.150 -58.412 1.00 67.61 C O
ATOM 10668 N GLU I 511 -18.078 11.713 -56.928 1.00 64.95 C N
ATOM 10669 CA GLU I 511 -18.673 12.822 -57.664 1.00 60.64 C C
ATOM 10670 CB GLU I 511 -18.175 14.162 -57.117 1.00 20.00 C C
ATOM 10671 CG GLU I 511 -18.700 14.509 -55.736 1.00 20.00 C C
ATOM 10672 CD GLU I 511 -18.061 15.767 -55.172 1.00 20.00 C C
ATOM 10673 OE1 GLU I 511 -17.166 16.329 -55.841 1.00 20.00 C O
ATOM 10674 OE2 GLU I 511 -18.506 16.237 -54.102 1.00 20.00 C O
ATOM 10675 C GLU 1 511 -18.377 12.729 -59.159 1.00 59.91 C C
ATOM 10676 O GLU 1 511 -19.245 13.008 -59.983 1.00 55.45 C O
ATOM 10677 N LEU 1 512 -17.122 12.450 -59.503 1.00 44.35 C N
ATOM 10678 CA LEU I 512 -16.712 12.392 -60.904 1.00 49.60 C C
ATOM 10679 CB LEU 1 512 -15.196 12.240 -61.021 1.00 20.00 C C
ATOM 10680 CG LEU I 512 -14.353 13.460 -60.658 1.00 20.00 C C
ATOM 10681 CD1 LEU 1 512 -12.894 13.181 -60.963 1.00 20.00 C C
ATOM 10682 CD2 LEU I 512 -14.831 14.678 -61.424 1.00 20.00 C C
ATOM 10683 C LEU 1 512 -17.396 11.239 -61.621 1.00 58.00 C C
ATOM 10684 O LEU I 512 -17.946 11.411 -62.708 1.00 55.11 C O
ATOM 10685 N LEU 1 513 -17.306 10.051 -61.036 1.00 57.91 C N
ATOM 10686 CA LEU 1 513 -17.901 8.870 -61.636 1.00 57.49 C C
ATOM 10687 CB LEU 1 513 -17.632 7.629 -60.774 1.00 20.00 C C
ATOM 10688 CG LEU 1 513 -16.169 7.179 -60.678 1.00 20.00 C C
ATOM 10689 CD1 LEU I 513 -15.992 6.055 -59.670 1.00 20.00 C C
ATOM 10690 CD2 LEU 1 513 -15.637 6.768 -62.042 1.00 20.00 C C
ATOM 10691 C LEU 1 513 -19.399 9.075 -61.852 1.00 58.78 C C
ATOM 10692 O LEU 1 513 -19.913 8.812 -62.940 1.00 59.88 C O
ATOM 10693 N HIS 1 514 -20.054 9.718 -60.888 1.00 60.07 C N
ATOM 10694 CA HIS 1 514 -21.494 9.975 -60.982 1.00 62.82 C C
ATOM 10695 CB HIS 1 514 -22.058 10.454 -59.635 1.00 20.00 C C
ATOM 10696 CG HIS 1 514 -21.878 9.472 -58.517 1.00 20.00 C C
ATOM 10697 ND1 HIS 1 514 -22.551 8.269 -58.465 1.00 20.00 C N
ATOM 10698 CE1 HIS I 514 -22.192 7.612 -57.376 1.00 20.00 C C
ATOM 10699 NE2 HIS 1 514 -21.304 8.342 -56.723 1.00 20.00 C N
ATOM 10700 CD2 HIS I 514 -21.104 9.517 -57.407 1.00 20.00 C C
ATOM 10701 C HIS 1 514 -21.799 10.989 -62.087 1.00 65.10 C C
ATOM 10702 O HIS 1 514 -22.898 11.002 -62.647 1.00 66.73 C O
ATOM 10703 N ASN I 515 -20.795 11.787 -62.441 1.00 63.45 C N
ATOM 10704 CA ASN I 515 -20.932 12.782 -63.499 1.00 56.53 C C
ATOM 10705 CB ASN I 515 -19.903 13.909 -63.317 1.00 20.00 C C
ATOM 10706 CG ASN I 515 -20.243 14.838 -62.159 1.00 20.00 C C
ATOM 10707 OD1 ASN I 515 -21.400 14.948 -61.756 1.00 20.00 C O
ATOM 10708 ND2 ASN I 515 -19.238 15.544 -61.652 1.00 20.00 C N
ATOM 10709 C ASN 1 515 -20.765 12.134 -64.868 1.00 60.06 C C
ATOM 10710 O ASN 1 515 -21.518 12.422 -65.799 1.00 66.48 C O
ATOM 10711 N VAL I 516 -19.829 11.197 -64.959 1.00 54.29 C N
ATOM 10712 CA VAL I 516 -19.617 10.460 -66.195 1.00 52.70 C C
ATOM 10713 CB VAL I 516 -18.407 9.523 -66.097 1.00 20.00 C C
ATOM 10714 CGI VAL I 516 -18.398 8.554 -67.267 1.00 20.00 C C
ATOM 10715 CG2 VAL I 516 -17.122 10.330 -66.063 1.00 20.00 C C
ATOM 10716 C VAL 1 516 -20.850 9.645 -66.551 1.00 60.10 C C
ATOM 10717 O VAL 1 516 -21.306 9.662 -67.693 1.00 61.55 C O
ATOM 10718 N ASN 1 517 -21.432 8.998 -65.549 1.00 69.10 C N
ATOM 10719 CA ASN 1 517 -22.648 8.224 -65.749 1.00 67.75 C C
ATOM 10720 CB ASN 1 517 -23.135 7.652 -64.421 1.00 20.00 C C
ATOM 10721 CG ASN 1 517 -22.254 6.530 -63.914 1.00 20.00 C C
ATOM 10722 OD1 ASN I 517 -21.467 5.954 -64.667 1.00 20.00 C O
ATOM 10723 ND2 ASN I 517 -22.368 6.226 -62.627 1.00 20.00 C N
ATOM 10724 C ASN 1 517 -23.751 9.051 -66.394 1.00 71.17 C C
ATOM 10725 O ASN 1 517 -24.535 8.544 -67.196 1.00 66.42 C O ATOM 10726 N ALA 1 518 -23.811 10.326 -66.028 1.00 72.11 C N
ATOM 10727 CA ALA 1 518 -24.811 11.232 -66.571 1.00 74.82 C C
ATOM 10728 CB ALA 1 518 -24.936 12.464 -65.692 1.00 20.00 C C
ATOM 10729 C ALA 1 518 -24.471 11.628 -68.004 1.00 70.11 C C
ATOM 10730 O ALA 1 518 -25.328 11.590 -68.886 1.00 65.18 C O
ATOM 10731 N GLY I 519 -23.212 11.989 -68.230 1.00 56.07 C N
ATOM 10732 CA GLY I 519 -22.709 12.224 -69.577 1.00 53.01 C C
ATOM 10733 C GLY I 519 -22.906 11.026 -70.483 1.00 63.58 C C
ATOM 10734 O GLY I 519 -23.221 11.174 -71.663 1.00 69.35 C O
ATOM 10735 N LYS 1 520 -22.776 9.833 -69.912 1.00 58.33 C N
ATOM 10736 CA LYS 1 520 -22.996 8.592 -70.647 1.00 53.44 C C
ATOM 10737 CB LYS 1 520 -22.655 7.389 -69.767 1.00 20.00 C C
ATOM 10738 CG LYS 1 520 -21.194 7.319 -69.368 1.00 20.00 C C
ATOM 10739 CD LYS 1 520 -20.915 6.097 -68.525 1.00 20.00 C C
ATOM 10740 CE LYS 1 520 -19.428 5.920 -68.314 1.00 20.00 C C
ATOM 10741 NZ LYS 1 520 -19.148 4.767 -67.417 1.00 20.00 C N
ATOM 10742 C LYS 1 520 -24.437 8.485 -71.121 1.00 58.24 C C
ATOM 10743 O LYS 1 520 -24.714 7.920 -72.179 1.00 48.60 C O
ATOM 10744 N SE I 521 -25.354 8.971 -70.293 1.00 67.19 C N
ATOM 10745 CA SE I 521 -26.772 8.995 -70.632 1.00 60.42 C C
ATOM 10746 CB SE I 521 -27.588 9.481 -69.436 1.00 20.00 C C
ATOM 10747 OG SE I 521 -27.281 10.830 -69.130 1.00 20.00 C O
ATOM 10748 C SER I 521 -27.047 9.892 -71.837 1.00 54.19 C C
ATOM 10749 O SER I 521 -27.767 9.506 -72.758 1.00 65.36 C O
ATOM 10750 N THR 1 522 -26.556 11.124 -71.770 1.00 50.09 C N
ATOM 10751 CA THR 1 522 -26.650 12.048 -72.892 1.00 57.59 C C
ATOM 10752 CB THR 1 522 -25.950 13.377 -72.579 1.00 20.00 C C
ATOM 10753 OG1 THR I 522 -24.538 13.159 -72.466 1.00 20.00 C O
ATOM 10754 CG2 THR I 522 -26.478 13.957 -71.275 1.00 20.00 C C
ATOM 10755 C THR I 522 -26.040 11.450 -74.153 1.00 59.16 C C
ATOM 10756 O THR 1 522 -26.682 11.416 -75.202 1.00 65.90 C O
ATOM 10757 N THR 1 523 -24.840 10.891 -74.020 1.00 52.59 C N
ATOM 10758 CA THR 1 523 -24.151 10.267 -75.148 1.00 42.19 C C
ATOM 10759 CB THR 1 523 -22.805 9.649 -74.725 1.00 20.00 C C
ATOM 10760 OG1 THR I 523 -23.027 8.645 -73.726 1.00 20.00 C O
ATOM 10761 CG2 THR I 523 -21.876 10.722 -74.172 1.00 20.00 C C
ATOM 10762 C THR I 523 -25.002 9.194 -75.822 1.00 48.90 C c
ATOM 10763 O THR I 523 -24.991 9.059 -77.047 1.00 63.19 c o
ATOM 10764 N ASN I 524 -25.694 8.395 -75.018 1.00 52.51 c N
ATOM 10765 CA ASN I 524 -26.597 7.386 -75.553 1.00 57.54 c c
ATOM 10766 CB ASN I 524 -27.089 6.458 -74.444 1.00 20.00 c c
ATOM 10767 CG ASN I 524 -26.002 5.533 -73.941 1.00 20.00 c c
ATOM 10768 OD1 ASN I 524 -25.000 5.316 -74.620 1.00 20.00 c o
ATOM 10769 ND2 ASN I 524 -26.153 5.050 -72.714 1.00 20.00 c N
ATOM 10770 C ASN I 524 -27.776 7.996 -76.302 1.00 54.12 c c
ATOM 10771 O ASN I 524 -28.076 7.601 -77.428 1.00 61.31 c o
ATOM 10772 N SER I 525 -28.372 9.027 -75.714 1.00 48.97 c N
ATOM 10773 CA SER I 525 -29.483 9.734 -76.336 1.00 64.81 c c
ATOM 10774 CB SER I 525 -29.930 10.885 -75.441 1.00 61.22 c c
ATOM 10775 OG SER I 525 -29.691 10.571 -74.078 1.00 85.90 c o
ATOM 10776 C SER I 525 -29.114 10.265 -77.713 1.00 69.67 c c
ATOM 10777 O SER I 525 -29.974 10.417 -78.580 1.00 72.60 c o
ATOM 10778 N LYS I 526 -27.853 10.647 -77.872 1.00 66.06 c N
ATOM 10779 CA LYS I 526 -27.365 11.130 -79.154 1.00 63.67 c c
ATOM 10780 CB LYS I 526 -26.043 11.874 -78.980 1.00 70.55 c c
ATOM 10781 CG LYS I 526 -26.196 13.332 -78.608 1.00 75.29 c c
ATOM 10782 CD LYS I 526 -24.898 13.870 -78.032 1.00 85.03 c c
ATOM 10783 CE LYS I 526 -25.144 15.017 -77.067 1.00 82.65 c c
ATOM 10784 NZ LYS I 526 -24.040 15.141 -76.075 1.00 73.89 c N
ATOM 10785 C LYS I 526 -27.182 9.975 -80.124 1.00 55.36 c c ATOM 10786 O LYS 1 526 -27.591 10.050 -81.283 1.00 70.69 C O
ATOM 10787 N ILE 1 527 -26.593 8.892 -79.634 1.00 57.52 C N
ATOM 10788 CA ILE 1 527 -26.355 7.723 -80.461 1.00 58.48 C C
ATOM 10789 CB ILE 1 527 -25.712 6.589 -79.650 1.00 57.00 C C
ATOM 10790 CGI ILE 1 527 -24.414 7.071 -78.993 1.00 49.07 C C
ATOM 10791 CD1 ILE 1 527 -23.516 7.882 -79.906 1.00 46.18 C C
ATOM 10792 CG2 ILE 1 527 -25.469 5.370 -80.530 1.00 52.63 C C
ATOM 10793 C ILE 1 527 -27.649 7.230 -81.097 1.00 65.20 C C
ATOM 10794 O ILE 1 527 -27.705 7.000 -82.304 1.00 66.48 C O
ATOM 10795 N TY 1 528 -28.705 7.141 -80.293 1.00 69.78 C N
ATOM 10796 CA TY 1 528 -30.027 6.783 -80.798 1.00 72.52 C C
ATOM 10797 CB TYR 1 528 -31.080 6.916 -79.695 1.00 73.16 C C
ATOM 10798 CG TYR 1 528 -30.768 6.138 -78.433 1.00 76.94 C C
ATOM 10799 CD1 TYR I 528 -31.402 6.444 -77.233 1.00 70.95 C C
ATOM 10800 CE1 TYR I 528 -31.123 5.739 -76.074 1.00 67.73 C C
ATOM 10801 CZ TYR 1 528 -30.200 4.712 -76.103 1.00 71.89 C C
ATOM 10802 OH TYR 1 528 -29.927 4.009 -74.954 1.00 75.44 C O
ATOM 10803 CE2 TYR I 528 -29.534 4.407 -77.273 1.00 77.03 C C
ATOM 10804 CD2 TYR I 528 -29.818 5.120 -78.431 1.00 77.84 C C
ATOM 10805 C TYR 1 528 -30.414 7.661 -81.985 1.00 71.63 C C
ATOM 10806 O TYR 1 528 -30.720 7.162 -83.069 1.00 84.20 C O
ATOM 10807 N HIS 1 529 -30.470 8.966 -81.748 1.00 67.69 C N
ATOM 10808 CA HIS 1 529 -30.934 9.902 -82.759 1.00 60.28 C C
ATOM 10809 CB HIS 1 529 -30.900 11.336 -82.218 1.00 67.84 C C
ATOM 10810 CG HIS I 529 -31.927 11.615 -81.162 1.00 88.54 C C
ATOM 10811 ND1 HIS 1 529 -32.439 12.875 -80.934 1.00 93.34 C N
ATOM 10812 CE1 HIS I 529 -33.289 12.828 -79.924 1.00 86.23 C C
ATOM 10813 NE2 HIS 1 529 -33.346 11.583 -79.486 1.00 91.95 C N
ATOM 10814 CD2 HIS I 529 -32.495 10.807 -80.235 1.00 93.77 C C
ATOM 10815 C HIS 1 529 -30.094 9.785 -84.029 1.00 63.30 C C
ATOM 10816 O HIS 1 529 -30.632 9.642 -85.127 1.00 61.02 C O
ATOM 10817 N ILE 1 530 -28.775 9.752 -83.867 1.00 59.79 C N
ATOM 10818 CA ILE 1 530 -27.886 9.457 -84.984 1.00 45.70 C C
ATOM 10819 CB ILE 1 530 -26.413 9.365 -84.536 1.00 40.57 C C
ATOM 10820 CGI ILE I 530 -25.854 10.764 -84.270 1.00 42.86 C C
ATOM 10821 CD1 ILE 1 530 -24.376 10.902 -84.570 1.00 51.01 C C
ATOM 10822 CG2 ILE I 530 -25.575 8.662 -85.596 1.00 35.31 C C
ATOM 10823 C ILE 1 530 -28.301 8.153 -85.660 1.00 57.52 C C
ATOM 10824 O ILE 1 530 -28.637 8.136 -86.845 1.00 71.18 C O
ATOM 10825 N GLU I 531 -28.485 7.122 -84.841 1.00 67.55 C N
ATOM 10826 CA GLU 1 531 -28.876 5.801 -85.321 1.00 69.79 C C
ATOM 10827 CB GLU 1 531 -29.114 4.869 -84.134 1.00 84.02 C C
ATOM 10828 CG GLU 1 531 -28.794 3.415 -84.402 1.00104.22 C C
ATOM 10829 CD GLU 1 531 -28.980 2.551 -83.170 1.00116.08 C C
ATOM 10830 OE1 GLU I 531 -28.474 2.927 -82.091 1.00118.71 C O
ATOM 10831 OE2 GLU I 531 -29.736 1.564 -83.255 1.00119.69 C O
ATOM 10832 C GLU 1 531 -30.145 5.890 -86.151 1.00 64.87 C C
ATOM 10833 O GLU 1 531 -30.218 5.343 -87.250 1.00 55.58 C O
ATOM 10834 N ASN 1 532 -31.177 6.489 -85.566 1.00 65.70 C N
ATOM 10835 CA ASN 1 532 -32.459 6.657 -86.240 1.00 64.16 C C
ATOM 10836 CB ASN 1 532 -33.475 7.303 -85.296 1.00 60.58 C C
ATOM 10837 CG ASN 1 532 -34.859 7.396 -85.905 1.00 67.75 C C
ATOM 10838 OD1 ASN I 532 -35.480 6.381 -86.221 1.00 53.59 C O
ATOM 10839 ND2 ASN I 532 -35.352 8.618 -86.072 1.00 61.81 C N
ATOM 10840 C ASN 1 532 -32.330 7.486 -87.517 1.00 72.17 C C
ATOM 10841 O ASN 1 532 -32.999 7.220 -88.517 1.00 85.75 C O
ATOM 10842 N GLU 1 533 -31.469 8.495 -87.470 1.00 79.68 C N
ATOM 10843 CA GLU 1 533 -31.248 9.372 -88.611 1.00 71.96 C C
ATOM 10844 CB GLU I 533 -30.422 10.590 -88.186 1.00 67.87 C C
ATOM 10845 CG GLU I 533 -30.518 11.797 -89.125 1.00 81.94 C C ATOM 10846 CD GLU I 533 -31.932 12.348 -89.256 1.00 92.79 C C ATOM 10847 OE1 GLU I 533 -32.529 12.729 -88.227 1.00 95.90 c o ATOM 10848 OE2 GLU I 533 -32.399 12.511 -90.403 1.00 93.14 c o ATOM 10849 C GLU I 533 -30.546 8.622 -89.738 1.00 68.54 c c ATOM 10850 O GLU I 533 -30.737 8.928 -90.914 1.00 79.29 c o ATOM 10851 N ILE I 534 ■29.742 7.631 -89.367 1.00 69.50 c N ATOM 10852 CA ILE I 534 -29.047 6.796 -90.342 1.00 72.55 c c ATOM 10853 CB ILE I 534 -27.786 6.137 -89.729 1.00 79.55 c c ATOM 10854 CGI ILE I 534 -26.779 7.205 -89.298 1.00 80.41 c c ATOM 10855 CD1 ILE I 534 -26.687 8.374 -90.254 1.00 89.38 c c ATOM 10856 CG2 ILE I 534 -27.138 5.186 -90.724 1.00 78.63 c c ATOM 10857 C ILE I 534 - 29.972 5.707 -90.883 1.00 74.92 c c ATOM 10858 O ILE I 534 29.725 5.139 -91.948 1.00 81.01 c o ATOM 10859 N ALA I 535 -31.028 5.411 -90.130 1.00 79.52 c N ATOM 10860 CA ALA I 535 -32.056 4.474 -90.573 1.00 82.64 c c ATOM 10861 CB ALA I 535 -32.890 4.001 -89.386 1.00 75.39 c c ATOM 10862 C ALA I 535 -32.956 5.093 -91.645 1.00 81.39 c c ATOM 10863 O ALA I 535 -33.323 4.435 -92.622 1.00 85.54 c o ATOM 10864 N A G I 536 -33.274 6.373 -91.474 1.00 78.41 c N ATOM 10865 CA ARG I 536 -34.100 7.098 -92.435 1.00 83.27 c c ATOM 10866 CB ARG I 536 -34.664 8.372 -91.804 1.00 84.58 C c ATOM 10867 CG ARG I 536 -35.623 8.123 -90.651 1.00103.24 C c ATOM 10868 CD ARG I 536 -36.750 9.145 -90.630 1.00114.72 C C ATOM 10869 NE ARG I 536 -36.250 10.513 -90.521 1.00117.80 C N ATOM 10870 CZ ARG I 536 -37.009 11.598 -90.638 1.00116.66 C C ATOM 10871 NH1 ARG I 536 -38.311 11.478 -90.863 1.00114.57 C N ATOM 10872 NH2 ARG I 536 -36.470 12.803 -90.520 1.00116.38 C N ATOM 10873 C ARG I 536 -33.323 7.440 -93.703 1.00 82.20 C C ATOM 10874 O ARG I 536 -33.838 7.298 -94.812 1.00 86.28 C O ATOM 10875 N ILE I 537 32.114 7.964 -93.532 1.00 77.08 C N ATOM 10876 CA ILE I 537 -31.219 8.194 -94.659 1.00 66.79 C C ATOM 10877 CB ILE I 537 -29.908 8.850 -94.204 1.00 64.76 C C ATOM 10878 CGI ILE I 537 -30.176 10.251 -93.649 1.00 66.92 C C ATOM 10879 CD1 ILE I 537 -29.017 10.829 -92.869 1.00 70.83 C C ATOM 10880 CG2 ILE I 537 -28.926 8.905 -95.354 1.00 51.02 C C ATOM 10881 C ILE I 537 - 30.900 6.892 95.397 1.00 74.94 C C ATOM 10882 O ILE I 537 ■30.628 6.898 96.599 1.00 97.16 C O ATOM 10883 N LYS I 538 ■30.959 5.777 - 94.675 1.00 75.09 c N ATOM 10884 CA LYS I 538 -30.769 4.462 -95.275 1.00 90.28 c c ATOM 10885 CB LYS I 538 -30.228 3.472 -94.240 1.00 93.73 c c ATOM 10886 CG LYS I 538 -29.538 2.255 -94.850 1.00 96.60 c c ATOM 10887 CD LYS I 538 -29.040 1.288 -93.786 1.00 95.37 c c ATOM 10888 CE LYS I 538 -28.132 0.235 -94.399 1.00100.63 c c ATOM 10889 NZ LYS I 538 -27.652 -0.753 -93.397 1.00 99.58 c N ATOM 10890 C LYS I 538 32.062 3.927 - 95.884 1.00102.20 c c ATOM 10891 O LYS I 538 ■32.083 2.839 - 96.461 1.00112.11 c o ATOM 10892 N LYS I 539 ■33.126 4.722 - 95.795 1.00105.15 c N ATOM 10893 CA LYS I 539 -34.422 4.355 -96.360 1.00105.65 c c ATOM 10894 CB LYS I 539 -35.548 4.745 -95.398 1.00110.12 c c ATOM 10895 CG LYS I 539 -36.926 4.269 -95.823 1.00113.31 c c ATOM 10896 CD LYS I 539 -38.013 4.785 -94.889 1.00114.26 c c ATOM 10897 CE LYS I 539 -39.395 4.373 -95.378 1.00118.39 c c ATOM 10898 NZ LYS I 539 -40.449 4.593 -94.352 1.00121.77 c N ATOM 10899 C LYS I 539 34.646 5.008 - 97.726 1.00108.88 c c ATOM 10900 O LYS I 539 ■35.717 4.876 - 98.321 1.00110.77 c o ATOM 10901 N LEU I 540 -33.612 5.675 - ■98.232 1.00111.50 c N ATOM 10902 CA LEU I 540 -33.668 6.309 -99.544 1.00110.31 c c ATOM 10903 CB LEU I 540 -33.272 7.777 -99.435 1.00101.19 c c ATOM 10904 CG LEU I 540 -34.219 8.611 -98.581 1.00 94.26 c c ATOM 10905 CD1 LEU I 540 -34.093 10.066 -98.978 1.00 86.40 c c ATOM 10906 CD2 LEU 1 540 -35.646 8.133 -98.783 1.00 84.54 C C
ATOM 10907 C LEU 1 540 -32.738 5.601-100.513 1.00118.37 C C
ATOM 10908 O LEU 1 540 -32.526 6.059-101.634 1.00116.71 C O
ATOM 10909 N ILE I 541 -32.163 4.493-100.056 1.00130.80 C N
ATOM 10910 CA ILE I 541 -31.273 3.686-100.882 1.00140.48 C C
ATOM 10911 CB ILE I 541 -29.821 4.210-100.840 1.00138.99 C C
ATOM 10912 CGI ILE 1 541 -29.770 5.686-101.240 1.00133.30 C C
ATOM 10913 CD1 ILE 1 541 -30.650 6.027-102.420 1.00136.26 C C
ATOM 10914 CG2 ILE I 541 -28.924 3.372-101.744 1.00136.12 C C
ATOM 10915 C ILE 1 541 -31.289 2.233-100.426 1.00144.97 C C
ATOM 10916 O ILE 1 541 -30.938 1.333-101.188 1.00145.83 C O
ATOM 10917 N GLY 1 542 -31.724 2.004 -99.191 1.00148.77 C N
ATOM 10918 CA GLY 1 542 -31.789 0.655 -98.645 1.00153.58 C C
ATOM 10919 C GLY 1 542 -33.208 0.136 -98.534 1.00160.45 C C
ATOM 10920 O GLY 1 542 -34.109 0.602 -99.233 1.00163.41 C O
ATOM 10921 N GLU 1 543 -33.412 -0.799 -97.611 1.00163.83 C N
ATOM 10922 CA GLU I 543 -34.718 -1.409 -97.392 1.00165.52 C C
ATOM 10923 CB GLU I 543 -34.576 -2.673 -96.538 1.00158.94 C C
ATOM 10928 C GLU 1 543 -35.680 -0.430 -96.729 1.00168.27 C C
ATOM 10929 O GLU 1 543 -35.373 0.753 -96.584 1.00167.37 C O
ATOM 10930 CI NAG J1535 24.849 -25.592 34.903 1.00 72.96 C
ATOM 10931 C2 NAG J1535 24.818 -27.046 34.438 1.00 83.63 C
ATOM 10932 N2 NAG J1535 23.774 -27.757 35.160 1.00 85.81 N
ATOM 10933 C7 NAG J1535 23.087 -28.774 34.642 1.00 87.77 C
ATOM 10934 07 NAG J1535 23.376 -29.307 33.573 1.00 89.34 O
ATOM 10935 C8 NAG J1535 21.991 -29.339 35.498 1.00 86.84 C
ATOM 10936 C3 NAG J1535 26.183 -27.682 34.695 1.00 85.86 C
ATOM 10937 03 NAG J1535 27.009 -27.488 33.569 1.00 84.14 O
ATOM 10938 C4 NAG J1535 26.823 -27.025 35.913 1.00 88.88 C
ATOM 10939 04 NAG J1535 27.730 -27.923 36.530 1.00 96.14 O
ATOM 10940 C5 NAG J1535 25.692 -26.643 36.863 1.00 85.57 C
ATOM 10941 C6 NAG J1535 26.185 -26.278 38.259 1.00 85.54 C
ATOM 10942 06 NAG J1535 27.307 -25.431 38.159 1.00 85.75 O
ATOM 10943 05 NAG J1535 24.941 -25.575 36.317 1.00 79.39 O
ATOM 10944 CI NAG J1536 29.076 -27.393 36.512 1.00101.26 C
ATOM 10945 C2 NAG J1536 29.807 -27.737 37.810 1.00103.37 C
ATOM 10946 N2 NAG J1536 30.222 -26.531 38.504 1.00104.36 N
ATOM 10947 C7 NAG J1536 30.339 -26.483 39.830 1.00104.07 C
ATOM 10948 07 NAG J1536 30.062 -27.429 40.566 1.00103.82 O
ATOM 10949 C8 NAG J1536 30.810 -25.183 40.413 1.00103.07 C
ATOM 10950 C3 NAG J1536 31.013 -28.638 37.568 1.00104.12 C
ATOM 10951 03 NAG J1536 31.411 -29.224 38.788 1.00103.63 O
ATOM 10952 C4 NAG J1536 30.689 -29.737 36.565 1.00104.68 C
ATOM 10953 04 NAG J1536 31.865 -30.456 36.266 1.00105.46 O
ATOM 10954 C5 NAG J1536 30.104 -29.166 35.277 1.00104.39 C
ATOM 10955 C6 NAG J1536 28.856 -29.920 34.835 1.00104.32 C
ATOM 10956 06 NAG J1536 28.929 -30.178 33.450 1.00104.22 O
ATOM 10957 05 NAG J1536 29.840 -27.780 35.384 1.00103.22 O
ATOM 10958 CI NAG J1545 -15.969 -4.075 -43.033 1.00 56.85 C
ATOM 10959 C2 NAG J1545 -16.105 -5.488 -42.448 1.00 66.44 C
ATOM 10960 N2 NAG J1545 -14.794 -6.111 -42.415 1.00 69.47 N
ATOM 10961 C7 NAG J1545 -13.913 -5.853 -41.453 1.00 72.43 C
ATOM 10962 07 NAG J1545 -14.178 -5.152 -40.481 1.00 73.31 O
ATOM 10963 C8 NAG J1545 -12.558 -6.484 -41.587 1.00 72.22 C
ATOM 10964 C3 NAG J1545 -17.084 -6.379 -43.216 1.00 68.81 C
ATOM 10965 03 NAG J1545 -17.443 -7.508 -42.449 1.00 68.22 O
ATOM 10966 C4 NAG J1545 -18.314 -5.557 -43.561 1.00 71.19 C
ATOM 10967 04 NAG J1545 -19.356 -6.295 -44.161 1.00 76.87 O
ATOM 10968 C5 NAG J1545 -17.827 -4.416 -44.429 1.00 67.79 C
ATOM 10969 C6 NAG J1545 -18.955 -3.707 -45.166 1.00 67.71 C ATOM 10970 06 NAG J1545 -19.545 -2.754 -44.311 1.00 67.33 O
ATOM 10971 05 NAG J1545 -17.181 -3.544 -43.536 1.00 62.66 O
ATOM 10972 CI NAG J1546 -20.251 -6.690 -43.101 1.00 83.18 C
ATOM 10973 C2 NAG J1546 -21.616 -5.983 -43.168 1.00 85.51 C
ATOM 10974 N2 NAG J1546 -21.766 -5.147 -41.990 1.00 84.12 N
ATOM 10975 C7 NAG J1546 -21.679 -3.817 -41.993 1.00 82.64 C
ATOM 10976 07 NAG J 1546 -21.413 -3.148 -42.990 1.00 81.92 O
ATOM 10977 C8 NAG J1546 -21.866 -3.149 -40.663 1.00 80.96 C
ATOM 10978 C3 NAG J1546 -22.846 -6.884 -43.261 1.00 87.47 C
ATOM 10979 03 NAG J1546 -23.679 -6.482 -44.325 1.00 87.96 O
ATOM 10980 C4 NAG J1546 -22.495 -8.356 -43.377 1.00 87.61 C
ATOM 10981 04 NAG J1546 -23.635 -9.125 -43.071 1.00 86.77 O
ATOM 10982 C5 NAG J1546 -21.399 -8.665 -42.371 1.00 87.12 C
ATOM 10983 C6 NAG J1546 -21.176 -10.167 -42.218 1.00 87.02 C
ATOM 10984 06 NAG J1546 -20.698 -10.439 -40.920 1.00 86.44 O
ATOM 10985 05 NAG J1546 -20.211 -8.081 -42.842 1.00 85.80 O
ATOM 10986 CI NAG J1525 19.621 34.609 -15.280 1.00 72.96 C
ATOM 10987 C2 NAG J1525 20.014 34.434 -16.749 1.00 83.63 C
ATOM 10988 N2 NAG J1525 21.459 34.306 -16.817 1.00 85.81 N
ATOM 10989 C7 NAG J1525 22.104 33.549 -17.705 1.00 87.77 C
ATOM 10990 07 NAG J1525 21.559 33.036 -18.682 1.00 89.34 O
ATOM 10991 C8 NAG J1525 23.597 33.493 -17.560 1.00 86.84 C
ATOM 10992 C3 NAG J1525 19.546 35.624 -17.590 1.00 85.86 C
ATOM 10993 03 NAG J1525 18.248 35.381 -18.082 1.00 84.14 O
ATOM 10994 C4 NAG J1525 19.548 36.890 -16.742 1.00 88.88 C
ATOM 10995 04 NAG J1525 19.800 38.032 -17.545 1.00 96.14 O
ATOM 10996 C5 NAG J1525 20.649 36.717 -15.706 1.00 85.57 C
ATOM 10997 C6 NAG J1525 20.983 38.020 -14.991 1.00 85.54 C
ATOM 10998 06 NAG J1525 19.792 38.678 -14.623 1.00 85.75 O
ATOM 10999 05 NAG J1525 20.253 35.757 -14.753 1.00 79.39 O
ATOM 11000 CI NAG J1526 18.686 38.953 -17.492 1.00101.26 C
ATOM 11001 C2 NAG J1526 19.171 40.401 -17.403 1.00103.37 C
ATOM 11002 N2 NAG J1526 18.643 41.051 -16.216 1.00104.36 N
ATOM 11003 C7 NAG J1526 19.298 42.039 -15.609 1.00104.07 C
ATOM 11004 07 NAG J1526 20.406 42.432 -15.972 1.00103.82 O
ATOM 11005 C8 NAG J1526 18.641 42.635 -14.399 1.00103.07 C
ATOM 11006 C3 NAG J1526 18.781 41.209 -18.636 1.00104.12 C
ATOM 11007 03 NAG J1526 19.553 42.388 -18.684 1.00103.63 O
ATOM 11008 C4 NAG J1526 19.007 40.409 -19.911 1.00104.68 C
ATOM 11009 04 NAG J1526 18.509 41.133 -21.014 1.00105.46 O
ATOM 11010 C5 NAG J1526 18.320 39.050 -19.846 1.00104.39 C
ATOM 11011 C6 NAG J1526 19.260 37.926 -20.265 1.00104.32 C
ATOM 11012 06 NAG J1526 18.612 37.103 -21.209 1.00104.22 O
ATOM 11013 05 NAG J1526 17.776 38.800 -18.564 1.00103.22 O
ATOM 11014 CI NAG K1535 41.248 18.154 31.115 1.00 72.96 C
ATOM 11015 C2 NAG K1535 41.855 19.316 30.338 1.00 83.63 C
ATOM 11016 N2 NAG K1535 43.088 18.851 29.728 1.00 85.81 N
ATOM 11017 C7 NAG K1535 43.469 19.184 28.498 1.00 87.77 C
ATOM 11018 07 NAG K1535 42.908 20.051 27.830 1.00 89.34 O
ATOM 11019 C8 NAG K1535 44.735 18.550 28.004 1.00 86.84 C
ATOM 11020 C3 NAG K1535 42.118 20.499 31.270 1.00 85.86 C
ATOM 11021 03 NAG K1535 40.974 21.322 31.315 1.00 84.14 O
ATOM 11022 C4 NAG K1535 42.448 20.012 32.677 1.00 88.88 C
ATOM 11023 04 NAG K1535 43.310 20.930 33.331 1.00 96.14 O
ATOM 11024 C5 NAG K1535 43.123 18.655 32.535 1.00 85.57 C
ATOM 11025 C6 NAG K1535 43.778 18.188 33.832 1.00 85.54 C
ATOM 11026 06 NAG K1535 43.027 18.627 34.942 1.00 85.75 O
ATOM 11027 05 NAG K1535 42.190 17.694 32.074 1.00 79.39 O ATOM 11028 CI NAG K1536 42.680 21.487 34.509 1.00101.26 C ATOM 11029 C2 NAG K1536 43.698 21.677 35.636 1.00103.37 C ATOM 11030 N2 NAG K1536 43.310 20.938 36.825 1.00104.36 N
ATOM 11031 C7 NAG K1536 44.214 20.505 37.702 1.00104.07 C
ATOM 11032 07 NAG K1536 45.425 20.656 37.545 1.00103.82 O
ATOM 11033 C8 NAG K1536 43.689 19.781 38.906 1.00103.07 C
ATOM 11034 C3 NAG K1536 43.900 23.146 35.994 1.00104.12 C
ATOM 11035 03 NAG K1536 45.102 23.286 36.719 1.00103.63 O
ATOM 11036 C4 NAG K1536 43.966 24.019 34.748 1.00104.68 C
ATOM 11037 04 NAG K1536 43.988 25.378 35.126 1.00105.46 O
ATOM 11038 C5 NAG K1536 42.782 23.769 33.821 1.00104.39 C
ATOM 11039 C6 NAG K1536 43.229 23.554 32.380 1.00104.32 C
ATOM 11040 06 NAG K1536 42.483 24.396 31.530 1.00104.22 O
ATOM 11041 05 NAG K1536 41.980 22.692 34.267 1.00103.22 O
ATOM 11042 CI NAG K1545 2.615 1.983 -49.407 1.00 56.85 C
ATOM 11043 C2 NAG Kl 545 2.918 2.869 -50.621 1.00 66.44 c
ATOM 11044 N2 NAG K 1545 1.785 3.731 -50.894 1.00 69.47 N
ATOM 11045 C7 NAG Kl 545 1.517 4.812 -50.168 1.00 72.43 C
ATOM 11046 07 NAG K1545 2.154 5.121 -49.163 1.00 73.31 o
ATOM 11047 C8 NAG Kl 545 0.302 5.589 -50.579 1.00 72.22 c
ATOM 11048 C3 NAG Kl 545 3.247 2.088 -51.890 1.00 68.81 c
ATOM 11049 03 NAG K 1545 3.890 2.929 -52.817 1.00 68.22 o
ATOM 11050 C4 NAG Kl 545 4.146 0.927 -51.513 1.00 71.19 c
ATOM 11051 04 NAG K 1545 4.688 0.219 -52.606 1.00 76.87 o
ATOM 11052 C5 NAG Kl 545 3.310 0.066 -50.596 1.00 67.79 c
ATOM 11053 C6 NAG K1545 3.861 -1.348 -50.446 1.00 67.71 c
ATOM 11054 06 NAG K 1545 4.940 -1.351 -49.538 1.00 67.33 o
ATOM 11055 05 NAG K1545 3.330 0.760 -49.372 1.00 62.66 o
ATOM 11056 CI NAG K1546 5.996 0.777 -52.858 1.00 83.18 c
ATOM 11057 C2 NAG Kl 546 7.149 -0.188 -52.527 1.00 85.51 c
ATOM 11058 N2 NAG K 1546 7.911 0.336 -51.403 1.00 84.12 N
ATOM 11059 C7 NAG Kl 546 8.044 -0.298 -50.234 1.00 82.64 c
ATOM 11060 07 NAG K 1546 7.581 -1.414 -50.007 1.00 81.92 o
ATOM 11061 C8 NAG Kl 546 8.880 0.392 -49.197 1.00 80.96 c
ATOM 11062 C3 NAG Kl 546 8.093 -0.539 -53.684 1.00 87.47 c
ATOM 11063 03 NAG K1546 8.280 -1.934 -53.775 1.00 87.96 o
ATOM 11064 C4 NAG Kl 546 7.594 0.007 -55.013 1.00 87.61 c
ATOM 11065 04 NAG K 1546 8.586 -0.124 -56.008 1.00 86.77 o
ATOM 11066 C5 NAG Kl 546 7.269 1.469 -54.777 1.00 87.12 c
ATOM 11067 C6 NAG Kl 546 7.145 2.266 -56.074 1.00 87.02 c
ATOM 11068 06 NAG K1546 7.707 3.548 -55.896 1.00 86.44 o
ATOM 11069 05 NAG K 1546 6.050 1.508 -54.073 1.00 85.80 o
ATOM 11070 CI NAG K1525 -29. .090 1.326 0.431 1.00 56.85 c
ATOM 11071 C2 NAG Kl 525 -30. .509 1.450 1.026 1.00 66.44 c
ATOM 11072 N2 NAG K1525 -30 .921 0.195 1.623 1.00 69.47 N
ATOM 11073 C7 NAG K1525 -30. .381 -0.257 2.752 1.00 72.43 c
ATOM 11074 07 NAG K1525 -29 .481 0.332 3.347 1.00 73.31 o
ATOM 11075 C8 NAG Kl 525 -30. .965 -1.518 3.317 1.00 72.22 c
ATOM 11076 C3 NAG K1525 -31. .621 1.959 0.102 1.00 68.81 c
ATOM 11077 03 NAG K1525 -32 .692 2.482 0.855 1.00 68.22 o
ATOM 11078 C4 NAG K1525 -31. .056 3.022 -0.817 1.00 71.19 c
ATOM 11079 04 NAG K1525 -32 .040 3.689 -1.591 1.00 76.87 o
ATOM 11080 C5 NAG Kl 525 -30. .031 2.269 -1.642 1.00 67.79 c
ATOM 11081 C6 NAG Kl 525 -29. .635 3.028 -2.906 1.00 67.71 c
ATOM 11082 06 NAG K1525 -28 .857 4.152 -2.561 1.00 67.33 o
ATOM 11083 05 NAG K1525 -28 .906 2.013 -0.814 1.00 62.66 o
ATOM 11084 CI NAG K1526 -32. .430 4.903 -0.902 1.00 83.18 c
ATOM 11085 C2 NAG Kl 526 -31. .984 6.181 -1.635 1.00 85.51 c
ATOM 11086 N2 NAG K1526 -30 .942 6.832 -0.859 1.00 84.12 N
ATOM 11087 C7 NAG Kl 526 -29. .678 6.943 -1.267 1.00 82.64 c
ATOM 11088 07 NAG K1526 -29 .276 6.528 -2.353 1.00 81.92 o
ATOM 11089 C8 NAG Kl 526 -28. .739 7.632 -0.321 1.00 80.96 c ATOM 11090 C3 NAG K1526 -33.070 7.210 -1.965 1.00 87.47 C
ATOM 11091 03 NAG K1526 -32.990 7.586 -3.320 1.00 87.96 O
ATOM 11092 C4 NAG K1526 -34.468 6.712 -1.644 1.00 87.61 C
ATOM 11093 04 NAG K1526 -35.385 7.783 -1.653 1.00 86.77 O
ATOM 11094 C5 NAG K1526 -34.395 6.107 -0.257 1.00 87.12 C
ATOM 11095 C6 NAG K1526 -35.779 5.918 0.354 1.00 87.02 C
ATOM 11096 06 NAG K1526 -35.724 6.194 1.736 1.00 86.44 O
ATOM 11097 05 NAG K1526 -33.754 4.862 -0.395 1.00 85.80 O
ATOM 11098 CI NAG L1535 -2.070 11.341 45.870 1.00 72.96 C
ATOM 11099 C2 NAG L1535 -3.565 11.622 45.740 1.00 83.63 C
ATOM 11100 N2 NAG L1535 -3.793 13.060 45.821 1.00 85.81 N
ATOM 11101 C7 NAG L1535 -4.706 13.721 45.104 1.00 87.77 C
ATOM 11102 07 NAG L1535 -5.570 13.168 44.424 1.00 89.34 O
ATOM 11103 C8 NAG L1535 -4.727 15.213 45.270 1.00 86.84 C
ATOM 11104 C3 NAG L1535 -4.303 10.883 46.855 1.00 85.86 C
ATOM 11105 03 NAG L1535 -4.575 9.563 46.441 1.00 84.14 O
ATOM 11106 C4 NAG L1535 -3.441 10.862 48.115 1.00 88.88 C
ATOM 11107 04 NAG L1535 -4.260 10.849 49.273 1.00 96.14 O
ATOM 11108 C5 NAG L1535 -2.549 12.100 48.077 1.00 85.57 C
ATOM 11109 C6 NAG L1535 -1.872 12.404 49.410 1.00 85.54 C
ATOM 11110 06 NAG L1535 -1.282 11.235 49.931 1.00 85.75 O
ATOM 11111 05 NAG L1535 -1.585 11.956 47.052 1.00 79.39 O
ATOM 11112 CI NAG L1536 -4.061 9.626 50.020 1.00101.26 C
ATOM 11113 C2 NAG L1536 -4.102 9.893 51.524 1.00103.37 C
ATOM 11114 N2 NAG L1536 -2.863 9.461 52.140 1.00104.36 N
ATOM 11115 C7 NAG L1536 -2.405 10.023 53.252 1.00104.07 C
ATOM 11116 07 NAG L1536 -2.958 10.972 53.807 1.00103.82 O
ATOM 11117 C8 NAG L1536 -1.111 9.476 53.773 1.00103.07 C
ATOM 11118 C3 NAG L1536 -5.265 9.179 52.199 1.00104.12 C
ATOM 11119 03 NAG L1536 -5.486 9.747 53.470 1.00103.63 O
ATOM 11120 C4 NAG L1536 -6.532 9.306 51.370 1.00104.68 C
ATOM 11121 04 NAG L1536 -7.534 8.514 51.963 1.00105.46 O
ATOM 11122 C5 NAG L1536 -6.309 8.841 49.937 1.00104.39 C
ATOM 11123 C6 NAG L1536 -6.864 9.838 48.932 1.00104.32 C
ATOM 11124 06 NAG L1536 -7.576 9.132 47.943 1.00104.22 O
ATOM 11125 05 NAG L1536 -4.947 8.581 49.669 1.00103.22 O
ATOM 11126 CI NAG L1545 -11.652 16.132 -42.376 1.00 56.85 C
ATOM 11127 C2 NAG L1545 -11.811 17.208 -43.449 1.00 66.44 C
ATOM 11128 N2 NAG L1545 -10.485 17.531 -43.934 1.00 69.47 N
ATOM 11129 C7 NAG L1545 -9.803 16.702 -44.718 1.00 72.43 C
ATOM 11130 07 NAG L1545 -10.291 15.689 -45.219 1.00 73.31 O
ATOM 11131 C8 NAG L1545 -8.341 16.997 -44.865 1.00 72.22 C
ATOM 11132 C3 NAG L1545 -12.475 18.463 -42.898 1.00 68.81 C
ATOM 11133 03 NAG L1545 -12.890 19.301 -43.953 1.00 68.22 O
ATOM 11134 C4 NAG L1545 -13.667 18.017 -42.071 1.00 71.19 C
ATOM 11135 04 NAG L1545 -14.509 19.077 -41.672 1.00 76.87 O
ATOM 11136 C5 NAG L1545 -13.113 17.218 -40.907 1.00 67.79 C
ATOM 11137 C6 NAG L1545 -14.125 17.020 -39.786 1.00 67.71 C
ATOM 11138 06 NAG L1545 -15.086 16.069 -40.180 1.00 67.33 O
ATOM 11139 05 NAG L1545 -12.727 15.986 -41.467 1.00 62.66 O
ATOM 11140 CI NAG L1546 -15.574 19.184 -42.644 1.00 83.18 C
ATOM 11141 C2 NAG L1546 -16.945 18.806 -42.055 1.00 85.51 C
ATOM 11142 N2 NAG L1546 -17.436 17.613 -42.723 1.00 84.12 N
ATOM 11143 C7 NAG L1546 -17.522 16.433 -42.114 1.00 82.64 C
ATOM 11144 07 NAG L1546 -17.214 16.256 -40.937 1.00 81.92 O
ATOM 11145 C8 NAG L1546 -18.068 15.302 -42.933 1.00 80.96 C
ATOM 11146 C3 NAG L1546 -18.033 19.883 -42.093 1.00 87.47 C
ATOM 11147 03 NAG L1546 -18.679 19.995 -40.846 1.00 87.96 O
ATOM 11148 C4 NAG L1546 -17.484 21.228 -42.533 1.00 87.61 C
ATOM 11149 04 NAG L1546 -18.538 22.132 -42.784 1.00 86.77 O ATOM 11150 C5 NAG L1546 -16.723 20..935 -43..810 1.00 87.12 C
ATOM 11151 C6 NAG L1546 -16.525 22. 183 -44. .663 1.00 87.02 C
ATOM 11152 06 NAG L1546 -17.041 21. .939 -45. .954 1.00 86.44 O
ATOM 11153 05 NAG L1546 -15.492 20. .356 -43. .444 1.00 85.80 O
ATOM 11154 CI NAG L1525 21.793 ■26. .723 -18. .244 1.00 56.85 C
ATOM 11155 C2 NAG LI 525 22.365 ■27. .060 -19. .634 1.00 66.44 C
ATOM 11156 N2 NAG LI 525 22.402 -25. .862 -20. .460 1.00 69.47 N
ATOM 11157 C7 NAG LI 525 23.351 ■24. .934 -20. .342 1.00 72.43 C
ATOM 11158 07 NAG LI 525 24.279 -25. .026 -19. .540 1.00 73.31 O
ATOM 11159 C8 NAG L1525 23.280 ■23. .766 -21. .282 1.00 72.22 C
ATOM 11160 C3 NAG L1525 21.624 ■28. 181 -20. .369 1.00 68.81 C
ATOM 11161 03 NAG L1525 22.407 -28. .687 -21. .427 1.00 68.22 O
ATOM 11162 C4 NAG LI 525 21.308 ■29. .275 -19. .364 1.00 71.19 C
ATOM 11163 04 NAG LI 525 20.761 -30. .454 -19. .918 1.00 76.87 O
ATOM 11164 C5 NAG LI 525 20.389 ■28. .631 -18. .348 1.00 67.79 C
ATOM 11165 C6 NAG L1525 19.627 ■29. .660 -17. .520 1.00 67.71 C
ATOM 11166 06 NAG L1525 20.442 -30. .144 -16. .478 1.00 67.33 O
ATOM 11167 05 NAG LI 525 21.225 -27. .824 -17. .551 1.00 62.66 O
ATOM 11168 CI NAG L1526 21.846 ■31. .384 -20. 124 1.00 83.18 C
ATOM 11169 C2 NAG L1526 21.792 ■32. .604 -19. 182 1.00 85.51 C
ATOM 11170 N2 NAG L1526 22.928 -32. .540 -18. .274 1.00 84.12 N
ATOM 11171 C7 NAG L1526 22.851 ■32. .639 -16. .945 1.00 82.64 C
ATOM 11172 07 NAG L1526 21.797 -32. .785 -16. .328 1.00 81.92 O
ATOM 11173 C8 NAG L1526 24.156 ■32. .563 -16. .207 1.00 80.96 C
ATOM 11174 C3 NAG L1526 21.773 ■33. .981 -19. .854 1.00 87.47 C
ATOM 11175 03 NAG L1526 20.751 -34. .790 -19. .316 1.00 87.96 O
ATOM 11176 C4 NAG L1526 21.648 ■33. .901 -21. .365 1.00 87.61 C
ATOM 11177 04 NAG L1526 21.965 -35. .150 -21. .938 1.00 86.77 O
ATOM 11178 C5 NAG L1526 22.647 ■32. .860 -21. .827 1.00 87.12 C
ATOM 11179 C6 NAG L1526 22.903 ■32. .944 -23. .327 1.00 87.02 C
ATOM 11180 06 NAG L1526 24.294 -32. .969 -23. .563 1.00 86.44 O
ATOM 11181 05 NAG L1526 22.108 -31. .604 -21. .499 1.00 85.80 O
END

Claims

CLAIMS What is claimed is:
1. A pre-fusion respiratory syncytial virus (RS V) F polypeptide comprising at least two introduced cysteine residues, wherein said cysteines are in close proximity to one another and form a disulfide bond that stabilizes the pre-fusion RSV F polypeptide.
2. The pre-fusion RSV F polypeptide of claim 1, wherein said cysteine mutations are not more than about 10 A away from each other.
3. The pre-fusion RSV F polypeptide of claim 1 or 2, wherein the HRB region and the DI and/or DII region contain an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residue in the HRB region and the introduced cysteine residue in the DI or DII region.
4. The pre-fusion RSV F polypeptide of claim 1 or 2, wherein the HRA region and the Dili region contain an introduced cysteine residue, and a disulfide bond is formed between the introduced cysteine residues in the HRA region and the Dili region.
5. The pre-fusion RSV F polypeptide of claim 1 or 2, wherein the HRA region contains at least two introduced cysteine residues, and a disulfide bond is formed between the introduced cysteine residues in the HRA region.
6. A pre-fusion respiratory syncytial virus (RSV) F polypeptide comprising a post-fusion modification selected from the group consisting of deletion of the HRA helix, deletion of the HRB helix, introduction of point mutations, addition of glycosylation sites and combinations thereof, wherein said post-fusion modification destabilizes the post-fusion conformation.
7. The pre-fusion RSV F polypeptide of claim 6, wherein said destabilizing post- fusion modification is deletion of the HRB helix.
8. The pre-fusion RSV F polypeptide of claim 7, further comprising deletion of the fusion peptide.
9. The pre-fusion RSV F polypeptide of claim 6, wherein said destabilizing post- fusion modification is addition of a glycosylation site.
10. The pre-fusion RSV F polypeptide of claim 9, wherein said glycosylation site is on a residue selected from the group consisting of position 173, position 175 and position 184.
11. A pre-fusion respiratory syncytial virus (RSV) F polypeptide comprising three RSV F monomers, wherein at least two of the monomers contain an introduced cysteine residue, said introduced cysteine residues are in close proximity to one another and form a disulfide bond that stabilizes the pre-fusion RSV F polypeptide.
12. The pre-fusion RSV F polypeptide of any one of claims 1-11, wherein the pre- fusion RSV F polypeptide is a soluble ectodomain of RSV F or a trimer of soluble ectodomain of RSV F.
13. A chimeric pre-fusion F protein comprising a stabilized F protein from a virus other than RSV that contains one or more neutralizing epitope of RSV F.
14. The chimeric pre-fusion F protein of claim 13, wherein said stabilized F protein is from a parainfluenza virus F polypeptide or a metapneumovirus virus F polypeptide.
15. The chimeric pre-fusion F protein of claim 13, wherein said stabilized F protein is a PIV5 pre-fusion F polypeptide or a NDV pre-fusion F polypeptide.
16. The chimeric pre-fusion F protein of any one of claims 13-15, wherein the stabilized F protein is the soluble ectodomain.
17. The chimeric pre-fusion F protein of any one of claims 13-16, wherein said neutralizing epitopes of RSV F are from the HRA region of RSV F.
18. The chimeric pre-fusion F protein of any one of claims 13-16, wherein the neutralizing epitopes are selcted from the group consisting of the epitopes that are recognized by motavizumab, palivizumab, mAb 11, mAb 151, mAb 1129, mAb 1153, mAb 1200, mAb 1214, mAb 1237, mAb 47F, mAb 7C2, mAb B4, Fab 19, mAb AK13A2, mAb 7.936, mAb 9.936, mAb 19, mAb 20, mAb 101F and combinations thereof.
19. The pre-fusion RSV F polypeptide or chimeric pre-fusion F protein of any one of claims 1-18, further comprising a heterologous oligomerization domain, an epitope, or a signal peptide.
20. The pre-fusion RSV F polypeptide or chimeric pre-fusion F protein of claim 19, wherein said heterologous oligomerization domain is a trimerization domain.
21. The pre-fusion RSV F polypeptide or chimeric pre-fusion F protein of claim 20 wherein the trimerization domain is from influenza hemagglutinin, SARS spike, HIV gp41, NadA, modified GCN4, GCN4 or ATCase.
22. An immunogenic composition comprising the pre-fusion RSV F polypeptide or chimeric pre-fusion F protein of any one of claim 1-21.
23. The immunogenic composition of claim 22, wherein said composition further comprises an adjuvant.
24. The immunogenic composition of claim 23, wherein the adjuvant is selected from the group consisting of: an aluminum salt, a squalene-in- water emulsion, a
benzonaphthyridine compound, a phospholipid compound, a small molecule
immunopotentiator and combinations of any of the foregoing.
25. An isolated nucleic acid encoding the pre-fusion RSV F polypeptide or chimeric pre-fusion F protein of any one of claims 1 - 21.
26. The isolated nucleic acid of claim 25, which is a self-replicating RNA molecule.
27. An immunogenic composition comprising the self-replicating RNA molecule of claim 26.
28. The immunogenic composition of claim 26, further comprising an RNA delivery system.
29. A method of inducing an immune response in a subject to RSV F comprising administering an immunogenic composition of any one of claims 22-24 to the subject.
29. A method of inducing an immune response in a subject to RSV F comprising administering an immunogenic composition of claim 27 or 28 to the subject.
PCT/US2012/037773 2011-05-13 2012-05-14 Pre-fusion rsv f antigens WO2012158613A1 (en)

Priority Applications (28)

Application Number Priority Date Filing Date Title
LTEP12722057.2T LT2707385T (en) 2011-05-13 2012-05-14 Pre-fusion rsv f antigens
ES12722057.2T ES2651143T3 (en) 2011-05-13 2012-05-14 RS prefusion F antigens
MX2013013133A MX351011B (en) 2011-05-13 2012-05-14 Pre-fusion rsv f antigens.
CN201280034429.1A CN103842374A (en) 2011-05-13 2012-05-14 Pre-fusion rsv f antigens
RU2013155485/10A RU2013155485A (en) 2011-05-13 2012-05-14 F RSV ANTIGENS IN BEFORE MERGING CONFORMATION
CA2835644A CA2835644C (en) 2011-05-13 2012-05-14 Pre-fusion rsv f antigens
BR112013029169-9A BR112013029169B1 (en) 2011-05-13 2012-05-14 POLYPEPTIDE F PRE-FUSION OF THE RESPIRATORY SYNCYCIAL VIRUS (RSV), IMMUNOGENIC COMPOSITION AND USE OF THE SAME
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US14/117,588 US20140248314A1 (en) 2011-05-13 2012-05-14 Pre-fusion rsv f antigens
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CY20201100283T CY1122826T1 (en) 2011-05-13 2020-03-26 PRE-FUSION RSV F ANTIGONS
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