JPWO2005022436A1 - Protein structure three-dimensional display system for displaying protein function expression mechanism - Google Patents

Abstract

Provided is a protein structure three-dimensional display system for displaying a protein function expression mechanism that can three-dimensionally understand the function and mechanism of a protein related to an enzyme and an information transmission system. A protein structure three-dimensional display system includes a protein database storing coordinate data of molecules constituting a protein as a record file for each protein molecule, and a read buffer means for reading and temporarily storing a plurality of files of the protein record file. , Display attribute setting means for setting display attributes for a plurality of files of the protein record file, and reading the plurality of files of the protein record file, and sequentially based on the display attributes associated with the files Display processing means for three-dimensionally displaying a protein structure based on coordinate data of molecules constituting the protein.

Description

  By utilizing protein science and bioinformatics (the field of analyzing biology using information processing technology) technology, the present invention provides three-dimensional functions and mechanisms of proteins, especially proteins related to enzymes and information transmission systems. As you can see, protein functions can be displayed in three dimensions by opening multiple protein structure data files at the same time and displaying the state of action by arrows, interrupted lines, straight lines, etc. The present invention relates to a protein structure three-dimensional display system for mechanism display.

  In order to investigate the properties of a new (unknown) substance physically or chemically, or to create a new substance artificially, the three-dimensional structure of the substance is determined by a technique such as an X-ray crystal analyzer or NMR. Then, information on the determined three-dimensional structure is accumulated in a database, and research and development are performed by using information of a protein data bank (PDB) that is the accumulated database.

  For this reason, information on the three-dimensional structure of the protein, which has been clarified by the X-ray crystallographic analysis of the protein, is registered in the PDB according to a predetermined data format. A protein has a three-dimensional structure formed by connecting a plurality of amino acids like a single chain and folding the chain in vivo. This three-dimensional structure data is registered in the PDB and stored in a usable state. Specifically, the PDB includes a protein name, a management number, an amino acid residue number that identifies an amino acid residue that constitutes the protein, information about each atom that constitutes each amino acid residue, and three-dimensional coordinate information (record data). ) Is registered.

  From the results of chemical research so far, it is known that there is a close relationship between the three-dimensional structure of substances and their functions. Therefore, in order to modify substances and create new functions, Searching for similar structures that exist in common in the three-dimensional structure of each substance, etc., analyzing the three-dimensional structure of each substance, and conducting research.

  For such analysis, software “RASMOL” that can display a three-dimensional structure of a protein three-dimensionally has been used by many researchers (see Non-Patent Document 1 and Non-Patent Document 2). This protein three-dimensional structure display software “RASMOL” can display the three-dimensional structure of protein biomolecules based on data described in a format corresponding to the protein database “PDB”.

  When displaying protein 3D structure with the software 3D structure display software “RASMOL”, the record data of each protein of PDB can be displayed one file at a time, but the 3D structure of multiple files can be displayed. It cannot be displayed sequentially in time series. Also, it does not include functions for expressing reactions between atoms and molecules such as catalytic reactions and information transmission.

  As this type of technology, as shown in Patent Document 1, conventionally, in order to evaluate how the interaction between individual local structures of protein molecules contributes to the formation of a three-dimensional structure, a computer is used. A protein molecule three-dimensional structure analysis apparatus that displays the relationship between local structures by using the same has been developed.

  In this protein molecular three-dimensional structure analyzer, the three-dimensional structure formation of proteins is based on the fact that side chains of amino acid residues having affinity for each other aggregate and the force to contact them is the main driving force. Whether or not is in contact is used as an index of the interaction between amino acid residues, and these are determined. In the dependency relationship display processing, the dependency relationship between local structures is displayed as a graphic representing a directed graph.

RASMOL; biomolecular graphis for all, Trends Biochem Sci. 20-SEPTEMBER 1995, p. 374-376 A dynamic look at structures; WWW-Entrez and the Molecular Modeling Database, Trends Biochem Sci. 21-JUNE 1996, p. 226-229 Kinimages-simple macromolecular graphics for interactive teaching and publication, Trends Biochem Sci. 19-MARCH 1994, p. 135-138 Japanese Patent Laid-Open No. 05-282381

  For this reason, conventionally, in order to express interatomic and intermolecular reactions such as catalytic reactions and information transmission, for example, as shown in FIG. 1, a “chair type” that more accurately represents the structure. In the schematic diagram, a symbolized molecule is displayed, and the catalytic mechanism is expressed by arrows or the like in the part of the molecule. In the display of the catalyst mechanism in such an expression form, since the three-dimensional structure is not taken into consideration, the content of the catalyst mechanism cannot be fully expressed, and a sufficient understanding for the catalytic mechanism of the enzyme molecule cannot be obtained. There is.

  Specifically, FIG. 1 is an example of a schematic diagram representing the catalytic mechanism of an enzyme. In this schematic diagram 200, appropriate molecular states 201 for expressing the catalytic mechanism are appropriately displayed, Draws the relationship between the molecular states of Here, a reversible process of the catalytic reaction in which the substrate (ligand) passes through the first intermediate and the second intermediate to the first product (ligand) and the second product (ligand) is expressed. It has become. However, since the three-dimensional structure is not considered in the expression form as described above, it cannot be expressed in sufficient detail such as a bonding relationship and an electron movement state between molecules.

  In the analysis of proteins, etc., it is assumed that a reaction with the same catalytic mechanism occurs due to the movement of electrons between molecules if they are between molecules having the same three-dimensional structure, but in the schematic diagram shown in FIG. There is a problem that such contents cannot be confirmed.

  The present invention has been made in order to solve the above-described conventional problems, and the object of the present invention is to provide a three-dimensional understanding of the functions and mechanisms of proteins involved in enzymes and information transmission systems. Provides a three-dimensional protein structure display system for displaying the protein function expression mechanism that can open multiple files of protein structure data at the same time and display the three-dimensional arrows for displaying the catalytic mechanism There is to do.

  (1) In order to achieve the above object, in the protein structure three-dimensional display system according to the present invention, a protein database storing coordinate data of molecules constituting a protein as a record file for each protein molecule; Reading buffer means for reading and temporarily storing a plurality of files of the protein record file; display attribute setting means for setting display attributes for the plurality of files of the protein record file; and reading the plurality of files of the protein record file And display processing means for three-dimensionally displaying the protein structure based on the coordinate data of the molecules constituting the protein based on the display attributes associated with the file.

  (2) Further, in addition to the feature of the protein structure three-dimensional display system of (1), the display attribute setting means is provided for a plurality of files of the protein record file. The same display attribute is set, and the display processing means displays a plurality of different protein structures with display attributes of enlargement, reduction, rotation, and translation so as to have the same viewpoint.

  (3) In the protein structure three-dimensional display system according to the present invention, in addition to the characteristics of the protein structure three-dimensional display system of (1) or (2), the protein structure displayed by the display processing means is further provided. An input means for specifying a plurality of atoms in a user operation input, and when the protein structure atom displayed by the display processing means is specified by a user operation input by the input means, the specified atom An interatomic relationship display processing means for performing an interatomic relationship display process for displaying a relationship between atoms, and coordinate data of each atom whose relationship is displayed by the interatomic relationship display process is included in the display attribute. Display attribute holding means for holding the display attribute in association with the protein record file is provided.

  (4) In the protein structure three-dimensional display system according to the present invention, in addition to the characteristics of the protein structure three-dimensional display system of (3), the interatomic relationship display processing means is three-dimensionally displayed by the display processing means. An arrow display processing means for performing an arrow display process for displaying an arrow between the specified atoms when an interacting atom is specified by a user operation input with the input means among the atoms of the protein structure The display attribute holding means includes the coordinate data of the identified atom on which the arrow is displayed in the display attribute and associates it with a protein record file to hold the display attribute.

  (5) Further, in the protein structure three-dimensional display system according to the present invention, in addition to the feature of the protein structure three-dimensional display system of (3), the interatomic relationship display processing means is three-dimensionally displayed by the display processing means. When the interacting atoms are identified by the user's operation input by the input means among the atoms of the displayed protein structure, a linear display that three-dimensionally displays a columnar line between the identified atoms Linear display processing means for performing processing, wherein the display attribute holding means includes the coordinate data of the specified atom in which the columnar straight line is three-dimensionally displayed in the display attribute and associates it with a protein record file The display attribute is retained.

  (6) Further, in the protein structure three-dimensional display system according to the present invention, in addition to the feature of the protein structure three-dimensional display system of (3), the interatomic relationship display processing means is three-dimensionally displayed by the display processing means. Among the atoms of the displayed protein structure, when the interacting atoms are specified by the user's operation input by the input means, the dots or pillars arranged at equal intervals between the specified atoms, or It comprises a discontinuous line display processing means for performing a discontinuous line display process for three-dimensionally displaying the combination, and the display attribute holding means is identified by displaying the point bodies or the pillars arranged at equal intervals or a combination thereof. The display attribute is held by including coordinate data of atoms in the display attribute and associating the coordinate data with a protein record file.

  As described above, according to the present invention, the relationship between the atoms in the protein structure can be easily visually confirmed by the arrow display processing means, straight line display processing means, or intermittent line display processing means provided in the interatomic relation display processing means. It is possible to do. The arrow display processing means, the straight line display processing means, and the intermittent line display processing means can be used alone or in any combination to display the relationship between the atoms. That is, in addition to the display in which the display of the relationship between atoms by each display processing means is combined in series, the display in a double line shape in which the display by each display processing means is combined in parallel is also possible. More specifically, a configuration in which an arrow and a straight line are combined in series or in parallel, a configuration in which an arrow and an interrupted line are combined in series or in parallel, and a combination of a straight line and an interrupted line in series or in parallel It is possible to display the relationship between the atoms in terms of the form.

  Each display form of the relationship between atoms displayed by the interatomic relationship display processing means (arrow display processing means, straight line display processing means, interrupted line display processing means, and combinations thereof) By arbitrarily defining the relationship so as to correspond to the relationship, the relationship between atoms can be easily confirmed visually, and the relationship between the atoms can be easily grasped.

  In the protein structure three-dimensional display system according to the present invention, the protein database stores coordinate data of molecules constituting the protein as a record file for each protein molecule, and the protein record is read from the protein database by the read buffer means. When a plurality of files are read and temporarily stored, the display attribute setting means sets display attributes for each of the plurality of protein record files, so that the display processing means passes the read buffer means to the protein record. A plurality of files are read, and protein structures based on coordinate data of molecules constituting the proteins are sequentially displayed in three dimensions based on display attributes associated with the files. Thus, according to the protein structure three-dimensional display system of the present invention, in order to display the catalytic mechanism of the enzyme protein, the interactive function of the protein (for example, information transmission system, etc.), etc. Is read and based on the display attributes associated with the file, the protein structure is sequentially displayed in three dimensions based on the coordinate data of the molecules that make up the protein. Can be displayed continuously. For this reason, the action mechanism of the catalyst and the like are appropriately displayed on the display screen.

  In addition, according to the protein structure three-dimensional display system of the present invention, when atoms interacting between the atoms of the displayed protein structure are specified by the user's operation input, the interatomic / intermolecular Relationships are displayed by marking with three-dimensional arrows, intermittent lines, straight lines (points or columns arranged at equal intervals, or a combination thereof) between atoms (display of forms connected by arrows, etc.) Therefore, the relationship between atoms is expressed appropriately.

  Hereinafter, an embodiment for carrying out the present invention will be described with reference to the drawings. FIG. 2 is a diagram showing an overall system configuration of the protein structure three-dimensional display system for displaying the protein function expression mechanism of the first embodiment according to the present invention. In FIG. 2, 101 is a database storing protein three-dimensional structure data, 102 is a three-dimensional structure / function display system, 103 is a display device, 104 is an input processing subsystem, 105 is a keyboard, and 106 is a pointing device mouse. is there.

  The database 101 stores information on the three-dimensional coordinates of molecules and atoms constituting the protein as protein three-dimensional structure data (PDB format). Data for display processing is displayed in accordance with display control data from the input processing subsystem 104 based on the three-dimensional coordinate information of molecules and atoms constituting the protein read by the three-dimensional structure / function display system 102 from the database 101. Processing is performed, and molecules and atoms are three-dimensionally displayed on the display device 103. As a display processing engine that performs advanced image information processing that displays molecular structure three-dimensionally from protein three-dimensional structure data, which is the main part of the three-dimensional structure / function display system 102, software "3D display of protein three-dimensional structure" “RASMOL” (Non-Patent Document 1, Non-Patent Document 2) is used.

  In this case, the display contents for three-dimensionally displaying the molecular structure on the display screen are three-dimensionally displayed on the display screen of the display device 103 according to the display control data output from the input processing subsystem 104. The input processing subsystem 104 receives an operation input for three-dimensional display in real time in accordance with data input based on the user input operation received from the keyboard 105 and the mouse 106 of the pointing device, and rotates the display viewpoint desired by the user. Display control data such as inversion and color change is supplied to the three-dimensional structure / function display system 102. The three-dimensional structure / function display system 102 displays the three-dimensional structure of molecules and atoms constituting the protein based on the display control data.

  As described above, the display control data supplied from the input processing subsystem 104 to the three-dimensional structure / function display system 102 is generated by the user's mouse operation or key input operation from the keyboard, and is used as a command as the three-dimensional structure / function. Although sent to the display system 102, the series of commands may be supplied from a storage device or a storage medium that is created and stored in advance as a script file.

  In this case, the input processing subsystem 104 is provided with an interpretation processing unit that interprets the contents of the script file, and is configured to sequentially interpret and execute a series of commands that are made into the script file. That is, the input processing subsystem 104 generates display control data for the three-dimensional structure / function display system 102 to control the display mode when the molecular structure is three-dimensionally displayed.

  FIG. 3 is a block diagram showing in detail the configuration of system elements in the three-dimensional structure / function display system of the protein structure three-dimensional display system. In FIG. 3, reference numeral 101 denotes a database storing protein three-dimensional structure data, 102 denotes a three-dimensional structure / function display system, 103 denotes a display device, and 104 denotes an input processing subsystem. Also, 11 is a file buffer, 12 is a display processing unit for performing three-dimensional display of molecular structure, 13 is a display attribute setting unit, 14 is a script file storage unit for temporarily storing a script file, and 15 is an arrow for three-dimensional display. An arrow display processing unit 16 for drawing 3, an intermittent line display processing unit 16 for drawing a 3D display intermittent line (dots or columns arranged at equal intervals, or a combination of these), 17 is a 3D display It is a straight line display processing unit that draws straight lines (cylindrical straight lines). Reference numeral 50 denotes an interatomic relationship display processing unit, and 51 denotes a display attribute holding unit.

  The database 101 in which protein three-dimensional structure data is stored, the three-dimensional structure / function display system 102, the display device 103, and the input processing subsystem 104 are the same as those described in the system configuration of the protein structure three-dimensional display system (FIG. 2). Similar system elements.

  As shown in FIG. 3, the three-dimensional structure / function display system 102 is mainly configured by a display processing unit 12 that performs a three-dimensional display process of a molecular structure. As other system elements, a file buffer 11, a display attribute setting, and the like. A script file storage unit 14 that temporarily stores a script file, an interatomic relationship display processing unit 50, and a display attribute holding unit 51 are provided. The interatomic relationship display processing unit 50 is provided with an arrow display processing unit 15, an intermittent line display processing unit 16, and a straight line display processing unit 17, which are controlled to interact with each other according to a user operation input 2. When one atom is specified, a process for displaying the relationship between the atoms is performed.

  That is, when the user specifies the protein structure atom displayed by the display processing unit 12 via the input processing subsystem 104 by the user's operation input, the interatomic relationship display processing unit 50 The interatomic relationship display process is performed to display the relationship. In this case, the interatomic relationship display processing unit 50 controls the arrow display processing unit 15, the intermittent line display processing unit 16, or the straight line display processing unit 17 to perform the display process. When such display processing is performed, the display attribute holding unit 51 associates the coordinate data of each atom whose relationship is displayed by the interatomic relationship display processing with the display attribute and associates it with the protein record file. The display attribute data (display control data) is held.

  The arrow display processing unit 15 performs a display process for drawing a three-dimensional display arrow, and the intermittent line display processing unit 16 is a point body such as a three-dimensional display small sphere, a column body such as a cylinder, or a combination thereof. The display process which draws intermittent lines, such as a dotted line, a broken line, and a chain line, is performed. The straight line display processing unit 17 performs display processing for drawing a three-dimensional display straight line.

  Although not shown, a control processing unit for controlling these system elements is provided, and the control processing unit is for displaying a three-dimensional structure of a protein that the user desires to display in response to a request from the user. Is obtained by accessing the database 101, and each system element is controlled according to the command script of the script file, and the molecular structure is displayed on the display screen of the display device 103 according to the display form desired by the user. Controls 3D display.

  In the database 101, coordinate data of molecules constituting a protein is stored as a record file for each protein molecule. The file buffer 11 reads and temporarily stores a plurality of protein record files to be displayed on the display screen. The display attribute setting unit 13 sets display attributes for each of a plurality of protein record files. The display attributes set for each record file are supplied to the display processing unit 12. The display processing unit performs display processing for three-dimensionally displaying the molecular structure in accordance with display attribute setting data (display control data) set for the record file.

  The display processing unit 12 sequentially uses a plurality of protein record files read into the file buffer 11 based on coordinate data of molecules constituting the protein based on display attributes associated with the record files. Display protein structure in three dimensions.

  In this case, for example, when the display attribute setting unit 13 sets the same display attribute for a plurality of record files, the display processing unit 12 displays a plurality of different protein structures when the molecular structure is three-dimensionally displayed. The molecular structure can be displayed by performing display control of enlargement, reduction, rotation, and translation so as to have the same viewpoint. When displayed in this way, the molecular structures of a plurality of different proteins can be displayed on the screen from the same viewpoint. The set display attribute data is stored and held in the display attribute holding unit 51.

  The arrow display processing unit 15, the intermittent line display processing unit 16, and the straight line display processing unit 17 in the interatomic relationship display processing unit 50 indicate the relationship between two atoms displayed on the display screen as an arrow in a three-dimensional display form, The display is marked with a 3D display form intermittent line or a 3D display form straight line. In the molecular structure (protein structure record file) displayed three-dimensionally on the display screen of the display device, for example, when specifying two atoms that mark the relationship between atoms, such as between interacting atoms, Specifically, the designation is performed by inputting the atomic number of each atom by keyboard operation. Alternatively, it is designated in advance by a script file. The atomic number of each atom can be confirmed on the display screen by operating the pointer cursor by operating the mouse on each atom of the molecular structure displayed on the display screen. Further, on the display screen, the position of the atom displayed three-dimensionally may be specified by selecting and pointing with the pointer cursor.

  When the display processing unit 12 displays the protein molecular structure three-dimensionally on the display screen, the arrow display processing unit 15 is activated, and a plurality of atoms in the displayed protein structure are specified by a user operation input. In other words, when the interacting atoms are identified by the user's operation input between the atoms of the displayed protein structure, the arrow display that displays the relationship between the atoms with the three-dimensional display arrows Process. By performing such display, the action mechanism in the molecular structure can be clearly displayed. In this case, the display attribute setting unit 13 is provided with a storage unit for temporarily holding display attributes. For example, the display processing is performed by the arrow display processing unit 15 of the interatomic relationship display processing unit 50, and the coordinate data of the identified interacting atoms is displayed in the display attribute of the record file of the protein displayed at that time. It is included and stored as display attribute data in association with the record file.

  The intermittent line display processing unit 16 displays a three-dimensional intermittent line that has a different display form from the three-dimensional display arrow performed by the arrow display processing unit 15. The intermittent line display process is performed by a process similar to the process performed by the arrow display processing unit 15. That is, a display is performed in which the relationship between the specified atoms is connected by the intermittent line of the three-dimensional display. Specifically, when atoms that interact with each other among the atoms in the protein structure displayed on the display screen are specified by the user's operation input, the point objects arranged at equal intervals between the atoms Displayed as a combined state by. As described later, the intermittent line display processing unit 16 is described as a dotted line mode in which small spheres as dot bodies are arranged at equal intervals in the drawing, but column bodies such as cylinders are arranged at equal intervals. You may employ | adopt the display form of the chain line which arranges the aspect of a broken line, and dot bodies, such as a small sphere, and column bodies, such as a cylinder, combining.

  The straight line display processing unit 17 displays a columnar body such as a three-dimensional display cylinder instead of the three-dimensional display arrow performed by the arrow display processing unit 15, similarly to the intermittent line display processing unit 16. Displays the relationship between the identified atoms by a column such as a three-dimensional cylinder. Specifically, when atoms interacting with each other between protein structure atoms displayed on the display screen are specified by a user's operation input, the atoms are separated by a columnar straight line such as a cylinder. Three-dimensional display is performed as the display state of the connection.

  Each display processing unit in the above-described interatomic relationship display processing unit 50, that is, the arrow display processing unit 15, the intermittent line display processing unit 16, the straight line display processing unit 17, and the display processing of the relationship between atoms by a combination thereof are as follows. When the interacting atom is specified by the user's operation input between the atoms of the protein structure displayed by the display processing unit 12, it is used to display the relationship between the atoms. .

  FIG. 4 is a time chart for explaining the control processing by the control processing unit of the three-dimensional structure / function display system that displays a plurality of files simultaneously in the opening order. This will be described with reference to FIG. When the control processing unit is activated and display processing of a plurality of protein structure record files is started, the database 101 is accessed according to the contents of the script described in the script file, and each file (three-dimensional structure record data of the corresponding protein ( File 1, File 2, File 3, File 4) are sequentially read from the database 101 into the file buffer 11. At this time, if the display attribute data of the protein structure record file to be displayed is set in the script file, three-dimensional display processing is performed on the display screen in accordance with the display control data of the display attribute. When display attribute data is not set, default display attribute data preset in the display attribute setting unit 13 is used.

  The three-dimensional display of the molecular structure by the display processing unit 12 is started when reading of the file buffer 11 of the last record file (File 4) is completed. The script file displays the three-dimensional structure data of the protein in the first record file (File 1) for which display has been previously instructed. At that time, the user changes the display form as desired by looking at the display screen. For example, the three-dimensional structure is moved by enlargement, reduction, rotation, translation, or the like. In that case, for example, a fixed mode for fixing the viewpoint is set. If the fixed mode is not set, the default automatic adjustment mode is set. Since the display attribute display control data is set in the display attribute setting unit 13, when an instruction is given to switch the display contents to the display of the protein structure data of the next record file (File 2), the display attribute data is displayed. The 3D structure data of the protein in the second record file (File 2) is displayed. Similarly, when an instruction is given to switch the display content to the display of the three-dimensional structure data of the protein in the next record file (File 3), the protein in the third record file (File 3) is next in accordance with the display attribute. The three-dimensional structure data is displayed. Subsequently, the protein three-dimensional structure data of the fourth record file (File 4) is displayed.

  In this way, multiple protein record files can be opened at the same time, and the display form of the 3D display of the protein molecular structure can be arbitrarily switched by each record file. Also, the display form can be the same or different. , Can be switched arbitrarily and displayed. Furthermore, when displaying the three-dimensional structure of these molecular structures, for example, the relationship between specific atoms that interact with each other can be marked and displayed with a three-dimensional display arrow, and the action mechanism and the like can be displayed accurately. In this case, the atom to be marked by the arrow display is specified by, for example, the user operating the pointing device mouse or keyboard input device.

  In the time chart of the control process shown in FIG. 4, it is instructed to display an arrow / dotted line when displaying the protein three-dimensional structure data of the second record file (File 2), and the third record It is shown that the instruction is given also when displaying the three-dimensional structure data of the protein in the file (File 3).

  Next, the display process of the arrow displayed three-dimensionally will be specifically described. 5 to 7 are diagrams illustrating an example of an operation for displaying an arrow on a display screen displaying protein three-dimensional structure data of one record file. As shown in FIG. 5, in the display screen 21, the three-dimensional structure data of the protein is displayed by one record file, and in the display screen 21, between the atoms that can be determined to be interacting is marked, When two atoms from the right side are specified and an arrow display is instructed, an arrow 22a is displayed between the two atoms as in the display screen 22 shown in FIG. As a result, on the display screen 22, an arrow 22a is displayed from atom to atom that interacts.

  If two atoms are specified between different atoms, an arrow 23a is displayed between the two atoms in the center of the screen on the display screen 23 as shown in FIG. In the molecular structure display processing performed by the display processing unit 12 here, the distance between two atoms is determined, and it is determined that atoms close to a predetermined value or more are bonded to each other, and the bond display processing is performed. Therefore, a bonding state is displayed between two atoms, and an arrow 23 a is displayed between the two atoms at the center of the display screen 23 together with the bonding state. The display / non-display of the combined state can be arbitrarily switched by a user command input, as will be described later.

  FIG. 8 is a diagram illustrating an example of a display screen in which two atoms are displayed in a three-dimensional dotted line display form instead of the arrow display. As shown in FIG. 8, on the display screen 24 displaying the protein three-dimensional structure data of one record file, three dotted lines (intermittent lines) 24a, 24b are formed between the two sets of two atoms specified by the instruction. , 24c are connected and displayed. In this way, even if there are multiple pairs, by specifying the interacting atoms and indicating those atoms, it is possible to display a dotted line or an arrow to show the relationship between them as a three-dimensional display. it can.

  FIG. 9 is a diagram for explaining in detail the display form of the arrow display for three-dimensional display. FIG. 10 is a diagram for explaining in detail the display form of intermittent line display for three-dimensional display. In the display of the arrow for three-dimensional display, as shown in FIG. 9, the atoms are displayed in a sphere, and the first atom 31 and the second atom 33 are connected by the arrow 32 for three-dimensional display. indicate. The arrow 32 is displayed as an object combining a tube and a cone for drawing an arc. As a result, the arrow is clearly displayed even when the display is changed in direction (viewpoint). In the three-dimensional display of the molecular structure, it is often done by changing the orientation of the molecular structure, but in that case, even if the direction of the set arrow is changed and displayed, the visibility is not good. There is no decline. 9 (b) shows a state where the display form of FIG. 9 (a) is rotated forward, and a display form which is further rotated forward from the display form shown in FIG. 9 (b) is shown in FIG. 9 (c). ). In this arrow display, the display color can be easily changed as necessary by providing color setting changing means (not shown) that can arbitrarily change the display color (color) of the arrow.

  As shown in FIG. 10, in the display form of the intermittent line display for three-dimensional display, three-dimensional dotted lines are displayed by arranging point bodies at regular intervals between atoms. In the 3D display of the interrupted line display, atoms are displayed on a sphere, so the dot for the dotted line should be displayed in a display form with a sufficiently small sphere compared to it, so as not to touch the atoms draw. Here, the first atom 41 and the second atom 43 are connected to each other by an intermittent line display 42 using a three-dimensional display of a dotted line. As a result, similarly to the arrow display of FIG. 9, the dotted line is clearly displayed even when the display is changed in direction (viewpoint). In this case, even if the direction of the set interrupted line display is changed and displayed, the visibility does not deteriorate. A state in which the second atom 43 is rotated forward from the display form of FIG. 10A is the display form shown in FIG. In this case, a display form in which the relationship between two atoms is displayed by the intermittent line display 42 of the three-dimensional display. In these intermittent line displays, by providing color setting changing means (not shown) that can arbitrarily change the display color of the intermittent line, the display color can be easily changed as necessary. In the case of straight line display as well, color setting change means (not shown) that can arbitrarily set and change the display color is provided.

  In the protein structure three-dimensional display system of the embodiment here, as described above, a plurality of protein record files stored in the database are opened simultaneously, and according to the content of the display attribute data set in the display attribute setting unit. 3D display of the molecular structure of the protein and comparison of each protein's 3D structure data. In order to deepen understanding, a display screen example in that case will be described. FIG. 11 is a diagram illustrating a change in the display screen when the viewpoint mode is set to the automatic adjustment mode, and FIG. 12 is a diagram illustrating a change in the display screen when the viewpoint mode is set to the fixed mode. It is a figure to do.

  When the viewpoint mode is set to the automatic adjustment mode, as shown in FIG. 11, when displaying the record file of the three-dimensional structure of the protein, from the state of displaying the first file like the display screen 25, When the display of the next file is instructed, the display screen 26 is displayed in the automatic adjustment mode display setting. This is because first, the entire three-dimensional structure of the protein is displayed, so that the coordinate system is changed and the magnification is reduced.

  On the other hand, when the viewpoint mode is set to the fixed mode, as shown in FIG. 12, when the record file of the protein three-dimensional structure is displayed, the first file is displayed as in the display screen 27. If the display of the next file is instructed from this state, it is displayed as the display screen 28, and the data of the immediately preceding display attribute is inherited and displayed in the same coordinate system at the same magnification. In this case, since the same atom constituting the molecule is displayed at the same position, the user can easily compare the three-dimensional structure of a plurality of different molecules. On the display screen 28, the display attribute associated with the next displayed record file is displayed in the setting state because the discontinuous line display is set between the interacting atoms. Such a discontinuous line display can display a transition state or the like in the catalytic reaction, and the states can be compared. When straight line display is set, a columnar straight line such as a cylinder is displayed instead of the dotted line described above.

  As described above, in the protein structure three-dimensional display system of the present embodiment, a plurality of protein record files stored in the database are opened simultaneously, and the molecules are displayed according to the contents of the display attributes set in the display attribute setting unit. The structure is displayed in three dimensions so that the user can compare the three-dimensional structure data of each protein. Therefore, in order to display the relationship between two atoms, processing such as three-dimensional display arrow display, straight line display, or intermittent line display is performed, but main part display processing that performs three-dimensional display processing of the molecular structure In this section, the coordinate data of each atom is discriminated according to protein three-dimensional structure data, and atoms that are close to a predetermined distance or more are considered to be in a bonded state, and the atoms are bound by a bar (cylindrical straight line) display. It is displayed as the state that was done. If there is binding information in the record file of the three-dimensional structure of the protein, the binding state is displayed in the molecular image when displaying the molecular structure according to the binding information. The display of these connection states can be arbitrarily switched according to the user's wishes.

  The binding state is displayed according to the binding information of the protein record file, but the display / non-display can be arbitrarily switched. In the analysis of molecular catalytic mechanism, the distance (closeness) between two atoms is important. It is also important to display the state of whether or not it is in a coupled state. The user refers to these displays, identifies the atoms that interact with each other, and sets the arrow display or the intermittent line display therebetween. For this reason, the protein structure three-dimensional display system of the present embodiment has a function that allows various changes in the display of the binding state in the display of the molecular structure.

  In addition, in the case of performing the three-dimensional display of the arrow, a display adjustment unit (FIG. 5) capable of adjustment that can be rotated and displayed around the straight line connecting the start point and the end point of the arrow while maintaining the display form of the arrow. Not shown). By this display adjustment means, the display state of the arrow for performing the three-dimensional display can be finely adjusted appropriately.

FIG. 13 to FIG. 16 are diagrams for explaining the processing for displaying the bonding state between atoms when displaying the molecular structure. FIG. 13 shows a display screen 29 in which the display processing unit displays the bonding state according to the interatomic distance, and FIG. 14 shows the display screen 30 when the atomic number display is also performed. The combined information (CONNECT line / PDB format) registered in the record file in this case is
CONNECT 2748 2746 6261
CONNECT 3131 6290
CONNECT 6261 6262 6270 2748 6272
CONNECT 6290 6285 3131
From this bond information, the 6261th atom and the 6290th atom are not bonded. Therefore, in the display of the combined state reflecting the combined information registered in such a record file, a display screen 42 is displayed as shown in FIG.

  In the display that does not reflect the bond information, the prescribed distance between the atoms is determined based on the coordinate information of each atom and the bond state is displayed. Therefore, as shown in the display screen 41 shown in FIG. Is displayed. By switching the display of the bond state, the bond state between the two atoms is set to, for example, the three-dimensional arrow display or the intermittent line display as described above, and the two atoms interact with each other. Can be marked to indicate that may work. In other words, by switching between displaying and hiding the bond status based on bond information, you can find such atoms, and when you find such atoms, set the 3D display arrow display or intermittent line display. Can be marked.

  In addition, each system element of the protein structure three-dimensional display system may be configured as a network system using an Internet mechanism. In this case, as the database 101, a protein data bank (PDB) that provides an information providing service on the network can be used, and a three-dimensional structure / function display system 102, a display device 103, an input processing subsystem 104, and the like. For example, a personal computer or a workstation connected to the Internet can be used. 17 and 18 show examples of display screens of the protein structure three-dimensional display system configured as a network system. The display screen 43 shown in FIG. 17 corresponds to the display screen 23 of FIG. 7 that performs arrow display of 3D display, and the display screen 44 shown in FIG. 18 performs intermittent line display of 3D display. This corresponds to the display screen 24 of FIG.

  Next, the arrow display processing of the arrow display processing unit 15 described above will be described. FIG. 19 is a flowchart for explaining the processing flow of the arrow display processing. As described above, in the arrow display process of the three-dimensional display, the start point and the end point of the arrow display are given by an instruction to specify two atoms, and the process is performed by giving an arrow display instruction. A description will be given assuming that processing is performed by receiving a command or script by a user input.

  As shown in FIG. 19, when the processing is started, first, the center position of the curved arrow is set as a default (step 301), and the atomic numbers of the starting point atom A and the ending point atom B are set by user input by a script or command. An instruction and a command instruction of an arrow display are given (step 302). Since the data for drawing is given, it is determined whether or not the two points of the start point and the end point and the center of the curve arrow set by default form a straight line (step 303). Since it cannot be drawn as an arrow, a straight arrow is drawn from atom A to atom B (step 304).

  If the two points and the center are not a straight line, a plane composed of the positions of two atoms and the center position of a curved arrow set by default is defined (step 305). The positional relationship between the start point and end point of the two atoms is discriminated, and a curved arrow is drawn corresponding to each of them (steps 306 to 309). Further, it is determined whether or not there is a user input for stopping drawing, and if a command for stopping drawing is input, drawing of an arrow is stopped (steps 310 to 311).

  Next, the intermittent line display process of the above-described intermittent line display processing unit 16 will be described. FIG. 20 is a flowchart for explaining the processing flow of the intermittent line display processing. Even in the intermittent line display process, the start point and the end point to be displayed are given by an instruction specifying two atoms, and the process is performed by giving a display instruction. Here, the process is accepted by a command or script by user input. Will be described.

  Since dotted lines are drawn as a sequence of dot bodies, the sphere spacing of the dot bodies (small spheres) is set as a default (step 321). When given an atomic number instruction and a command line display command (step 322), dots (small spheres) are displayed at equal intervals between the two atoms, except for the distance of the van der Waals radius. In this manner, a dotted line is drawn (step 323). It is determined whether or not there is a user input for stopping drawing, and if a command for stopping drawing is input, drawing of an arrow is stopped (steps 324 to 325).

  21 to 24 are diagrams showing examples of script file descriptions. As described above, the display attribute (display control data) for displaying the three-dimensional structure of each protein is given by being described as a script file of a series of command strings including file operations. Since the display process of the molecular structure by the command sequence of the script file is not directly related to the present invention, the detailed description thereof will be omitted, but the command process is roughly performed as follows. These processes are the same as the processes in the protein three-dimensional structure display software “RASMOL”.

The record file of the 3D structure data of the molecular structure is read and the display process based on the data is performed as follows.
(1) A PDB format file is read. It is assumed that one molecular model is described for one file, not corresponding to a plurality of NMR models.
(2) The interatomic bond is automatically determined based on the interatomic distance. Also, the secondary structure is determined using the DSSP algorithm.

The lines to be read in the PDB format file and the data items to be acquired are as follows.
(A). The “HEADER” line is read and each data item of “classification, date, PDB code” is acquired.
(B) The “COMPND” line is read, and the “molecule name” data item is read. In this case, if the first “COMPND” line does not start with “MOL_ID:”, columns 11 to 70 are acquired. If the first “COMPND” line starts with “MOL_ID:”, 22 to 70 columns are acquired.
(C) The “SOURCE” line is read, and the “species” data item is read. In this case, if the first “SOURCE” line does not start with “MOL_ID:”, columns 11 to 70 are acquired. When the first “SOURCE” line starts with “MOL_ID:”, if there is a SOUR line starting with “ORGANISM_SCIENTIFIC:” after that, 33 to 70 columns are obtained, and a SOUR line starting with “ORGANISM_COMMON:” If there is, obtain 29-70 columns. If both, get both.
(D) Read the “ATOM, HETATM” line and read “Atom ID, Atom Name, AltLoc, Residue Name, chainID, Residue ID, Insertion Code, Spatial Coordinate x, Spatial Coordinate y, Spatial Coordinate z, Occupancy, Import each data item of “Temperature Factor”.
(E) The “CONNECT” line is read and “bond start atom ID (columns 7 to 11), bond end atom ID (columns 12 to 16), bond end atom ID (columns 17 to 21), bond end atom ID (column 22-26), bond termination atom ID (columns 27-31), ". In this case, if a plurality of Alternate locations are specified, the one with the largest occupation ratio is used as a default.

Interatomic bond determination process (1) General bond The interatomic distance (Å) is calculated for all atom pairs in the molecule, and it is determined that the bonds are bonded when the following conditions are satisfied.
0.4Å <interatomic distance <(sum of shared radii of two atoms) + 0.56Å
(2) Backbone formation The Cα atoms of the same chain are virtually combined in order. However, when the interatomic distance is 4.20 mm or more, it is not bonded.
(3) Disulfide bond The interatomic distance (Å) is calculated for S atom pairs of all cysteine residues in the molecule, and determined to be bonded when the following conditions are satisfied.
Interatomic distance <3.0 mm

(4) Hydrogen bond determination process a. For proteins,
1. Determine the position of the hydrogen atom. The N—H distance is 1 angstrom and the direction is parallel to the C—O: bond of the previous residue.
2. Only when the distance between the Cα atom and the Cα atom is 9 angstroms.
3. The binding energy is calculated by the following formula.
E = (332 / ε) (q1q2 / R12) (kcal / mol)
Where ε is the dielectric constant,
q1q2 is the charge in units of elementary charge e0 R12 is the distance (unit: Angstrom)
It is.
4). Correction processing based on calculation result of binding energy When E> −500 kcal / mol, E = 0.
5). For each residue, two bonds are retained in ascending order of binding energy.

b. In the case of DNA For all AT pairs and CG pairs that are not the same chain, the minimum distance within 5 angstroms between the purine skeleton N1 atom and the pyrimidine skeleton N3 atom is found and regarded as a bond.
2. The remaining hydrogen bonds are treated in each of the AT and CG pairs.

Secondary structure estimation process (1) α-helix structure If two or more situations in which hydrogen bonds exist between residues separated by a certain interval (specified by pitch) appear continuously, it is regarded as an α-helix structure.
(2) β sheet structure Search for a hydrogen bond pattern using three consecutive residues as one unit. If it matches the pattern, the middle residue of the three consecutive residues is considered a β sheet structure.
(3) Turn structure The angle κ is calculated for each residue. When κ> 70 °, residue 3 is considered a turn structure.

  In the above description, the display processing units of the arrow display processing unit 15, the straight line display processing unit 17, and the intermittent line display processing unit 16 in the interatomic relationship display processing unit that performs processing for displaying the relationship between the atoms of the protein structure are as follows. Each system element has been described as an independent system element, but by combining them, the display by each system element is combined in series, and the display by each system element is combined in a double line display. You can also That is, according to a form in which arrows and straight lines are combined in series or in parallel, a form in which arrows and interrupted lines are combined in series or in parallel, and a form in which straight lines and interrupted lines are combined in series or in parallel, It is possible to display the relationship between atoms in the protein structure. Thereby, when displaying the relationship between the atoms of a some protein structure, it can be set as the display which distinguished each relationship. Thereby, it can come to confirm now visually.

  In addition, each display form displayed in the interatomic relationship display processing unit (arrow display processing unit, straight line display processing unit, intermittent line display processing unit, and combinations thereof) should correspond to the relationship between atoms in advance. By arbitrarily defining the relationship, it is possible to visually confirm the relationship between different kinds of atoms, and it becomes possible to grasp the relationship very easily.

  Since this system can display three-dimensional mechanisms such as time-series enzyme functions and information transmission, it can be used to develop drugs and new protein functions through molecular modeling. .

  In addition, the protein structure three-dimensional display system of the present invention can open a plurality of protein three-dimensional structure data record files, display the three-dimensional molecular structure three-dimensionally, and display the three-dimensional structure data of the plurality of files from the same viewpoint. It is possible to display three-dimensional display of arrows, straight lines, or intermittent lines between two atoms, so that the relationship between molecules and atoms such as proteins, enzymes, and information transfer proteins can be displayed in a three-dimensional manner in time series. be able to. The arrow display is expressed as a tube, cone, etc., and can be displayed as an arrow from any direction in three dimensions. Even if the viewing angle is changed, the relationship between molecules and atoms is uniform. Can be displayed.

FIG. 1 is a diagram showing an example of a schematic diagram expressing the catalytic mechanism of an enzyme.
FIG. 2 is a diagram showing an overall system configuration of a protein structure three-dimensional display system for displaying a protein function expression mechanism according to the present invention.
FIG. 3 is a block diagram showing in detail the configuration of system elements in the three-dimensional structure / function display system of the protein structure three-dimensional display system.
FIG. 4 is a time chart for explaining a control process by a control processing unit of a three-dimensional structure / function display system that displays a plurality of files simultaneously in the order of opening.
FIG. 5 is a first diagram illustrating an example of an operation for displaying an arrow on a display screen displaying protein three-dimensional structure data of one record file.
FIG. 6 is a second diagram illustrating an example of an operation for displaying an arrow on a display screen displaying protein three-dimensional structure data of one record file.
FIG. 7 is a third diagram illustrating an example of an operation for displaying an arrow on a display screen displaying the protein three-dimensional structure data of one record file.
FIG. 8 is a diagram showing an example of a display screen displaying a three-dimensional dotted line between two atoms.
FIG. 9 is a diagram for explaining in detail the display form of the arrow display for three-dimensional display.
FIG. 10 is a diagram for explaining in detail the display form of the interrupted line display for three-dimensional display.
FIG. 11 is a diagram illustrating a change in the display screen when the viewpoint mode is set to the automatic adjustment mode.
FIG. 12 is a diagram for explaining a change in the display screen when the viewpoint mode is set to the fixed mode.
[FIG. 13] FIG. 13 is a first diagram for explaining a process for displaying a bonding state between atoms when displaying a molecular structure.
FIG. 14 is a second diagram for explaining the process for displaying the bonding state between atoms when displaying the molecular structure.
FIG. 15 is a third diagram for explaining the process for displaying the bonding state between atoms when displaying the molecular structure.
FIG. 16 is a fourth diagram illustrating a process for displaying the bonding state between atoms when displaying a molecular structure.
FIG. 17 is a first diagram showing a display screen example of a protein structure three-dimensional display system configured as a network system.
FIG. 18 is a second diagram showing a display screen example of a protein structure three-dimensional display system configured as a network system.
FIG. 19 is a flowchart illustrating a process flow of an arrow display process.
FIG. 20 is a flowchart for explaining the processing flow of the intermittent line display processing.
FIG. 21 is a first diagram showing a description example of a script file.
FIG. 22 is a second diagram showing a description example of a script file.
FIG. 23 is a third diagram showing a description example of a script file.
FIG. 24 is a fourth diagram showing a description example of a script file.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 File buffer 12 Display process part 13 Display attribute setting part 14 Script file memory | storage part 15 Arrow display process part 16 Intermittent line display process part 17 Straight line display process part 50 Interatomic relation display process part 51 Display attribute holding part 101 Database 102 Three-dimensional Structure / function display system 103 Display device 104 Input processing subsystem 105 Keyboard 106 Mouse

Claims (6)

A protein database storing coordinate data of molecules constituting the protein as a record file for each protein molecule;
Read buffer means for reading and temporarily storing a plurality of files of the protein record file;
Display attribute setting means for setting a display attribute for each of the plurality of files of the protein record file;
A display processing means for reading a plurality of files of the protein record file, and displaying three-dimensionally the protein structure based on the coordinate data of the molecules constituting the protein sequentially based on the display attribute associated with the file;
A protein structure three-dimensional display system comprising: The protein structure three-dimensional display system according to claim 1,
The display attribute setting means sets the same display attribute for a plurality of files of the protein record file,
The protein structure three-dimensional display system, wherein the display processing means displays a plurality of different protein structures with display attributes of enlargement, reduction, rotation, and translation so as to have the same viewpoint. The protein structure three-dimensional display system according to claim 1 or 2, further comprising:
Input means for specifying a plurality of atoms in the protein structure displayed by the display processing means by a user's operation input;
An atom for performing interatomic relationship display processing for displaying a relationship between atoms when the atoms of the protein structure displayed by the display processing means are specified by a user operation input by the input means Inter-relationship display processing means;
Display attribute holding means for holding the display attribute in association with the protein record file by including the coordinate data of each atom in which the relationship is displayed by the interatomic relationship display processing in the display attribute;
A protein structure three-dimensional display system comprising: The protein structure three-dimensional display system according to claim 3,
The interatomic relation display processing means is specified when an interacting atom is specified by a user operation input from the input means among the atoms of the protein structure three-dimensionally displayed by the display processing means. Comprising an arrow display processing means for performing an arrow display process for displaying an arrow between atoms;
The display attribute holding means includes the coordinate data of the identified atom on which the arrow is displayed in the display attribute, associates it with a protein record file, and holds the display attribute. Original display system. The protein structure three-dimensional display system according to claim 3,
The interatomic relation display processing means is specified when an interacting atom is specified by a user operation input from the input means among the atoms of the protein structure three-dimensionally displayed by the display processing means. Straight line display processing means for performing straight line display processing for three-dimensionally displaying columnar straight lines between atoms,
The display attribute holding means includes the coordinate data of the identified atom on which the columnar straight line is three-dimensionally displayed in the display attribute, associates the data with a protein record file, and holds the display attribute. Feature protein structure 3D display system. The protein structure three-dimensional display system according to claim 3,
The interatomic relation display processing means is specified when an interacting atom is specified by a user operation input from the input means among the atoms of the protein structure three-dimensionally displayed by the display processing means. It comprises a discontinuous line display processing means for performing a discontinuous line display process for three-dimensionally displaying point bodies or pillars arranged at equal intervals between atoms or a combination thereof,
The display attribute holding means includes the coordinate data of the specified atom in which the point bodies or the columnar bodies or the combinations thereof arranged at equal intervals are displayed in the display attribute and associates them with the protein record file. A protein structure three-dimensional display system characterized by retaining display attributes.

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