CN103049677B - A kind of computing method processing Small molecular and protein interaction - Google Patents
A kind of computing method processing Small molecular and protein interaction Download PDFInfo
- Publication number
- CN103049677B CN103049677B CN201110315297.7A CN201110315297A CN103049677B CN 103049677 B CN103049677 B CN 103049677B CN 201110315297 A CN201110315297 A CN 201110315297A CN 103049677 B CN103049677 B CN 103049677B
- Authority
- CN
- China
- Prior art keywords
- protein
- file
- docking
- smaller ligand
- small molecular
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The present invention relates to a kind of computing method processing Small molecular and protein interaction, comprise the following steps: (1) reads in protein and smaller ligand file data; (2) atomic type in protein and smaller ligand is judged; (3) position of random initializtion smaller ligand and angle; (4) run SearchProtein algorithm, optimize coordinate and the angle of smaller ligand, Chemscore formula is as evaluation function; (5) stop calculating after reaching maximum iteration time; (6) analysis result, the coordinate in RMSD, docking free energy Δ G and docking site, Output rusults.Compared with prior art, the present invention has and accomplishes have effect to make the advantages such as rapidly judgement to time between pollutant and biomacromolecule.
Description
Technical field
The present invention relates to a kind of calculating toxicology field, especially relate to a kind of computing method processing Small molecular and protein interaction.
Background technology
Growing along with human society, the mankind faced by environmental problem more serious.Various work, agricultural effluent, waste gas, waste sludge discharge enter the public environment that the mankind live, often containing many harmful compounds in these " three wastes ".At present, there is the discharge of many countries and regions to " three wastes " limit and forbid in the world, strict restriction has been made to the content of pollutant in environment, made relevant legal norm and injure from it to protect human body.Pollutant, to the hurtful process of human body, is that pollutant enters in body, with some important protein bound process in human body.These combined albumen, occupies the albumen of critical role often in the life process of people.After contaminant molecule and protein combination, have two kinds of behaviors, one, the structure of protein is changed, the change of structure often causes protein function to change, and makes it lose or changes original function.Under normal conditions, the existence of pollutant can affect the change of Secondary structure content; They are two years old, the contaminated thing of avtive spot of protein occupies, some functional molecules cannot be in conjunction with, thus cause some to have the material of key effect to be synthesized or to transform to health, human body the most for want of these important substance that should be synthesized and suffering damage.
The importance of pollutant and protein interaction research is particularly outstanding.Focusing on of research: first from the aspect of macroscopic view, which kind of impact pollutant causes to protein, the how insulting health of this impact.Secondly from microcosmic point, how the mechanism that pollutant and protein impact be.Microcosmic point combines with macroscopic aspect, by the comprehensive visual angle thoroughly making us obtain pollutant toxicity, people are made to evade pollutant, and strengthen the environmental consciousness of people, various circles of society are impelled to pay attention to the problem of environmental pollution, strengthen environmental renovation and stop pollution dynamics, finally make earth environment more healthy.
Chemistry, refers to by the problem in computing method solution chemical field.Computing method in chemistry cover various method.Different according to the system of scientist's research, multiple different computing method can be adopted.The most frequently used computing method are molecular mechanics and quantum chemistry calculation.The Macroscopic physical that what the object of chemistry was clearer and more definite is in order to obtain research object or chemical property.This macroscopic property can be divided into two classes: one, the static balancing character of object, the binding constant of such as two material effects, the average potential energy of an individual system or object radial distribution function in a liquid; Its two be dynamically, non-equilibrium nature, the phase transformation of such as object, macromolecular conformation change, the motion of Small molecular in cell membrane or nanotube.
In fact, the various character of a macromolecular system be the average of the quantum state that shows of this macromolecular various particulate of composition, and the unique channel obtaining particulate quantum state solves schrodinger equation.This is because schrodinger equation, whole character of particulate are implied.When finite time, a limited capability, it is impossible for carrying out ab iitio with schrodinger equation to each particulate of system, there is no need especially, so be necessary to propose one method more simply and effectively, obtain system character comparatively reliably.In order to solve the problem, propose Monte Carlo simulation approach and Molecular Dynamics method applies in the field of chemistry.To sum up, computing method can the static balancing character of forecasting object well.And then obtain reliable pollutant toxicity data.
Summary of the invention
Object of the present invention be exactly in order to overcome above-mentioned prior art exist defect and a kind of computing method processing Small molecular and protein interaction are provided.
Object of the present invention can be achieved through the following technical solutions:
Process computing method for Small molecular and protein interaction, it is characterized in that, comprise the following steps:
(1) protein and smaller ligand file data is read in;
(2) atomic type in protein and smaller ligand is judged;
(3) position of random initializtion smaller ligand and angle;
(4) run SearchProtein algorithm, optimize coordinate and the angle of smaller ligand, Chemscore formula is as evaluation function; ChemScore evaluation function is that the people such as Eldridge proposed in 1997.In program herein, just employ the function of ChemScore function as heat-supplied.ChemScore energy function is marked by the energy of following formula to part and protein:
ΔG
binding＝ΔG
0+ΔG
hbondS
hbond+ΔG
metalS
metal+ΔG
lipoS
lipo+ΔG
rotH
rot
(5) stop calculating after reaching maximum iteration time;
(6) analysis result, the coordinate in RMSD (root mean-square deviation amount), docking free energy Δ G and docking site, Output rusults.
Described part file comprises the type information of the type of atom, coordinate and key.
Position and the angle of described random initializtion smaller ligand are specially:
The position of smaller ligand and angle are around activated centre
scope in random to produce, and undertaken searching for and docking calculating by Presearch algorithm.
Described Presearch algorithm is docked with protein by first wife's body of protein, finds avtive spot and obtains original docking free energy Δ G
0, read in protein and original molecule part file data, judge the atomic type in protein and former ligand molecular, the position of random initializtion smaller ligand and angle; Protein molecule adds polarity hydrogen, and calculates Coleman's electric charge, preserved the file that suffix is called pdbqs, Small molecular through hydrogenation, calculated charge, and save as pdbq file after determining rotatable key; Utilize mkdpf4 order to generate the lattice point Parameter File required for docking, suffix is called .gpf, opens this file, grid element center is revised as the coordinate at avtive spot center; Dpf file is generated with mkdpf4 order.
Described SearchProtein algorithm is the molecular docking carrying out pollutant Small molecular and protein, and obtain docking free energy Δ G, read in protein and original molecule part file data, judge the atomic type in protein and former ligand molecular, the position of random initializtion smaller ligand and angle; Protein molecule adds polarity hydrogen, and calculates Coleman's electric charge, preserved the file that suffix is called pdbqs, Small molecular is through hydrogenation, and calculated charge, saves as pdbq file after determining rotatable key; Utilize mkdpf4 order to generate the lattice point Parameter File required for docking, suffix is called .gpf, opens this file, grid element center is revised as the coordinate at avtive spot center; Dpf file is generated with mkdpf4 order.
Compared with prior art, the present invention has can accomplish have effect to make rapid judgement to time between pollutant and biomacromolecule, is conducive to improving production efficiency.This key problem in technology principle is simple, and suggestion for operation, easily learns, and can be used widely in all fields.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1
The present invention is divided into Presearch and SearchProtein two functional modules.Mainly utilize ANSIC++ language compilation, under may operate in Windows and (SuSE) Linux OS.Have source program and header file 18 in routine package, main flow is: reading in of acceptor and ligand molecular, is mainly mol2 file layout; Acceptor and ligand molecular pre-service, mainly atomic type, appointment of the rotatable key of single shaft etc.PreSearch program needs to prepare presearch.txt file before operation; Then carry out random initializtion to Small molecular, Small molecular initialized location is around activated centre
scope in random to produce; Then Presearch is utilized to carry out searching for and docking calculating.Calculate the coordinate in the RMSD (root mean-square deviation amount) of docking, docking free energy Δ G and docking site.Set up Protein Data Bank, utilize SearchProtein module to carry out reverse docking experiment to Small molecular and large molecule.After SearchProtein program computation, can spanned file.File contains the energy of each docking and the coordinate in docking site.Also separately having file to provide respectively, Δ G docks evaluation of estimate and small molecule contaminants with Δ G0 and initial ligand docks evaluation of estimate.
Application definition input file, mainly defines acceptor molecule filename, ligand molecular filename, Initialization Center coordinate, initiation parameter, searching algorithm kind, searching algorithm parameter etc.Except acceptor molecule filename, ligand molecular filename must be specified, other parameters can be specified, and also can Use Defaults, and the use of program is easier to be easy-to-use.
The operation of program: in ToxicitySearch program, the three-dimensional coordinate x at the variable of the main optimization mainly center of smaller ligand, y and z, three Descartes angle d of ligand molecular, β and γ, its major calculations step is: (1) reads in protein and smaller ligand file, mainly SYBYLmol2 file layout, the type of the type containing atom in file, coordinate and key; (2) atomic type in protein and smaller ligand is judged; (3) position of random initializtion smaller ligand and angle; (4) run SearchProtein algorithm, optimize coordinate and the angle of smaller ligand, Chemscore formula is as evaluation function; (5) reach maximum iteration time, stop calculating; (6) analysis result, calculates RMSD, Output rusults.
Embodiment 2
The method of the protein acceptor that a kind of PFOS of searching may disturb, utilize reverse docking procedure PreSearch and reverse docking procedure SearchProtein, from self-built protein acceptor storehouse, have found 4 kinds of albumen to be combined with PFOS, these albumen are phosphodiesterase 4 D catalytic domain, urokinase catalyst territory, II type carbonic anhydrase and IV type dipeptidyl peptidase, and the simple analysis situation of PFOS at these protein active sites.Its detailed process is as follows:
PreSearch program needs to prepare presearch.txt file before operation.
./PreSearch-ppresearch.txt-lresult.log-oenergy.txt
Calculate 10 times at work, make the evaluation of energy average.1a2c.mol2 and 1a2c-l.mol2 represents the mol2 file of protein and the mol2 file of part respectively.After often completing the calculating of 1 protein, program can generate result.log file and energy.txt file.Result.log file have recorded the RMSD (root mean-square deviation amount) of docking in detail, docks the coordinate in free energy and docking site.
Summarize the free energy Δ G (last row representative adds the energy because of flexibility loss) of each docking and the coordinate at docking center, site, and this file is also as the input file of SearchProtein program.
The input file of SearchProtein is above-mentioned energy.txt file, but needs to add lastrow " ligandPFOS.mol2 " in file beginning.Need during operation to input following order:
./SearchProtein-penergy.txt-lresult.log-ofinalenergy.txt
After SearchProtein program computation, result.log file and finalenergy.txt file can be generated.Result.log file contains the energy of each docking and the coordinate in docking site.What finalenergy.txt then provided that Δ G docks evaluation of estimate and PFOS with Δ G0 and initial ligand respectively docks evaluation of estimate.
Embodiment 3
A kind of research pollutant 2, the method of 4-d and human albumin HAS interaction mechanism, as in embodiment 1 mention, utilize docking procedure PreSearch, find out 2,4-D may replace androgen and the position of estrogen on HSA, disturb this two kinds of hormone transports in human body, affect its function of bringing into normal play, sex hormone dysequilibrium in body may be made, and 2, the 4-D possibilities had an impact to the transport of thyroxine on haemocyanin are very little.
We are with close three molecules 2 of the interpretation of result result of Presearch docking, 4-D, estrogen, operative condition after androgen and HSA dock, docking the activated centre chosen is IIA avtive spot, it is worth mentioning that, in repeated multiple times calculating 2, during the Conjugated free energy of 4-D and HSA, find one with phenomenon special during other molecular dockings, the convergence of docking free energy value and two values instead of the value that calculate when 2,4-D and HSA docks mutually, these two values are respectively-34.0kJ/mol and-37.4kJ/mol.And comprising estrogen, androgen all only converges on a value at interior most molecules.
We are by four kinds of molecules, five kinds of situations are placed on figure and represent, for the secondary structure schematic diagram near HSA avtive spot, position when four kinds of Small molecular docking are the most stable in avtive spot, green and cyan is 2, position under 4-D two states, blue and purple is the position of estradiol and testosterone, and pink is thyroxine.Can find out, the position of two kinds of sex hormone is all below activated centre, and the position of 2,4-D is on the upper side, and thyroxine molecule is longer, runs through upper and lower, so combine the most stable.
Above-mentioned is can understand and apply the invention for the ease of those skilled in the art to the description of embodiment.Person skilled in the art obviously easily can make various amendment to these embodiments, and General Principle described herein is applied in other embodiments and need not through performing creative labour.Therefore, the invention is not restricted to embodiment here, those skilled in the art are according to announcement of the present invention, and the improvement made for the present invention and amendment all should within protection scope of the present invention.
Claims (1)
1. process computing method for Small molecular and protein interaction, it is characterized in that, comprise the following steps:
(1) protein and smaller ligand file data is read in;
(2) atomic type in protein and smaller ligand is judged;
(3) position of random initializtion smaller ligand and angle;
(4) run SearchProtein algorithm, optimize coordinate and the angle of smaller ligand, Chemscore formula is as evaluation function;
(5) stop calculating after reaching maximum iteration time;
(6) analysis result, the coordinate in RMSD, docking free energy Δ G and docking site, Output rusults;
Described part file comprises the type information of the type of atom, coordinate and key;
Position and the angle of described random initializtion smaller ligand are specially:
The position of smaller ligand and angle are around activated centre
scope in random to produce, and undertaken searching for and docking calculating by Presearch algorithm;
Described Presearch algorithm is docked with protein by first wife's body of protein, finds avtive spot and obtains original docking free energy Δ G
0, read in protein and original molecule part file data, judge the atomic type in protein and former ligand molecular, the position of random initializtion smaller ligand and angle; Protein molecule adds polarity hydrogen, and calculates Coleman's electric charge, preserved the file that suffix is called pdbqs, Small molecular through hydrogenation, calculated charge, and save as pdbq file after determining rotatable key; Utilize mkdpf4 order to generate the lattice point Parameter File required for docking, suffix is called .gpf, opens this file, grid element center is revised as the coordinate at avtive spot center; Dpf file is generated with mkdpf4 order;
Described SearchProtein algorithm is the molecular docking carrying out pollutant Small molecular and protein, and obtain docking free energy Δ G, read in protein and pollutant Small molecular file data, judge the atomic type in protein and pollutant Small molecular, the position of random initializtion smaller ligand and angle; Protein molecule adds polarity hydrogen, and calculates Coleman's electric charge, preserved the file that suffix is called pdbqs, Small molecular is through hydrogenation, and calculated charge, saves as pdbq file after determining rotatable key; Utilize mkdpf4 order to generate the lattice point Parameter File required for docking, suffix is called .gpf, opens this file, grid element center is revised as the coordinate at avtive spot center; Dpf file is generated with mkdpf4 order.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110315297.7A CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110315297.7A CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103049677A CN103049677A (en) | 2013-04-17 |
| CN103049677B true CN103049677B (en) | 2015-11-25 |
Family
ID=48062311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110315297.7A Expired - Fee Related CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103049677B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3203401A4 (en) * | 2014-09-30 | 2018-08-08 | Osaka University | Free energy calculation device, method, program, and recording medium with said program recorded thereon |
| CN107301327A (en) * | 2017-05-17 | 2017-10-27 | 华南理工大学 | A kind of method that use computer simulation metal complex interacts with DNA |
| WO2020168507A1 (en) * | 2019-02-21 | 2020-08-27 | 深圳晶泰科技有限公司 | Molecular docking cloud computing process control method |
| CN110007067A (en) * | 2019-03-11 | 2019-07-12 | 江苏理工学院 | A kind of protein molecule docking detection device |
| CN110148438B (en) * | 2019-04-12 | 2023-03-21 | 中山大学 | Zinc enzyme docking method based on optimal geometric matching |
| CN111613275B (en) * | 2020-05-26 | 2021-03-16 | 中国海洋大学 | Drug molecular dynamics result analysis method based on rmsd multi-feature |
| CN111933222A (en) * | 2020-08-04 | 2020-11-13 | 云南中烟工业有限责任公司 | Compound cooling degree judging method |
| CN114974399A (en) * | 2021-04-27 | 2022-08-30 | 中国科学院深圳先进技术研究院 | Method, system and computer readable carrier for dynamic analysis of protein-small molecule interactions |
| CN114627971B (en) * | 2022-03-18 | 2023-10-31 | 北京有竹居网络技术有限公司 | Data processing method and device for solid system |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101470776A (en) * | 2007-06-27 | 2009-07-01 | 弗·哈夫曼-拉罗切有限公司 | Systems and methods for mapping binding site volumes in macromolecules |
| CN102156823A (en) * | 2011-02-18 | 2011-08-17 | 复旦大学 | Method for screening compound with targeted action on inactive conformation of protein kinase |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6823267B2 (en) * | 2000-09-12 | 2004-11-23 | The Johns Hopkins University | Structural prediction of allosterism |
-
2011
- 2011-10-17 CN CN201110315297.7A patent/CN103049677B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101470776A (en) * | 2007-06-27 | 2009-07-01 | 弗·哈夫曼-拉罗切有限公司 | Systems and methods for mapping binding site volumes in macromolecules |
| CN102156823A (en) * | 2011-02-18 | 2011-08-17 | 复旦大学 | Method for screening compound with targeted action on inactive conformation of protein kinase |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103049677A (en) | 2013-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103049677B (en) | A kind of computing method processing Small molecular and protein interaction | |
| Zong et al. | First assessment of NO x sources at a regional background site in North China using isotopic analysis linked with modeling | |
| Hakami et al. | High-order, direct sensitivity analysis of multidimensional air quality models | |
| Li et al. | “New” reactive nitrogen chemistry reshapes the relationship of ozone to its precursors | |
| Abel et al. | Response of power plant emissions to ambient temperature in the eastern United States | |
| Lohman et al. | Modeling mercury in power plant plumes | |
| Carino et al. | Site-selective Cu deposition on Pt dendrimer-encapsulated nanoparticles: correlation of theory and experiment | |
| Sun et al. | Assessing the performance of gas collection systems in select Chinese landfills according to the LandGEM model: drawbacks and potential direction | |
| Lv et al. | Properties and atmospheric implication of methylamine–sulfuric acid–water clusters | |
| Harding et al. | Structural isomers and reactivity for Rh6 and Rh6+ | |
| Choi et al. | Assessment of transboundary ozone contribution toward South Korea using multiple source–receptor modeling techniques | |
| Yau et al. | Quantifying the impact of anthropogenic atmospheric nitrogen deposition on the generation of hypoxia under future emission scenarios in Chinese coastal waters | |
| Tarasova et al. | Estimating chemical footprint: contamination with mercury and its compounds | |
| Moosavi et al. | Carbon dioxide in monoethanolamine: Interaction and its effect on structural and dynamic properties by molecular dynamics simulation | |
| Cao et al. | Species packing and the latitudinal gradient in beta-diversity | |
| Larsen et al. | Ammonia exchange between the atmosphere and the surface waters at two locations in the Chesapeake Bay | |
| Ghysels et al. | Calculating reaction rates with partial Hessians: Validation of the mobile block Hessian approach | |
| Zhang et al. | Impacts of chlorine emissions on secondary pollutants in China | |
| Shen et al. | A machine-learning-guided adaptive algorithm to reduce the computational cost of integrating kinetics in global atmospheric chemistry models: application to GEOS-Chem versions 12.0. 0 and 12.9. 1 | |
| Cheruvu et al. | A spectral finite volume transport scheme on the cubed-sphere | |
| Heller et al. | Hopping and jumping between potential energy surfaces | |
| McNamara et al. | Structure and reactivity of dinitrogen pentoxide in small water clusters studied by electronic structure calculations | |
| Shoaib et al. | Adsorptions of formic and acetic acids on ice surface: Surface binding configurations and a possibility of interfacial proton transfer | |
| Tejero et al. | Hydrogen abstraction by soybean lipoxygenase-1. Density functional theory study on active site models in terms of Gibbs free energies | |
| Jing et al. | Quantum mechanical effect in protein–ligand interaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151125 Termination date: 20171017 |