KR100773055B1 - System and method for searching materials interfacing with proteins based on interfaceome and recording medium therefor - Google Patents

Abstract

A system, a method and a recording medium for searching materials interfacing with proteins based on interfaceome are provided to search materials interfacing with proteins more accurately and rapidly from database including information about interfaceome between proteins and other subject materials. A system for searching materials interfacing with proteins based on interfaceome comprises a controlling part(110); a database(120) which stores information about proteins, interfaceome and compounds; I/O interface(130); a device for extracting interfaceome(140) which generates a three dimensional structure of the proteins by referencing the database in accordance with inputting of an amino acid sequence of the protein to be searched, extracts the surface structure from the three dimensional structure and matches the surface structure with the each of the stored interfaceome to extract the interfaceome matched with a predetermined value; an interfacing material extracting device(150) which extracts the material having the interfaceome corresponding to the interfaceome of the protein to be searched from the database; a docking energy calculation device(170) which docks the material selected from the interfaceome of the protein to be searched and database and calculates the energy of the material during docking; and a storing unit(180). The system further comprises a lead material selecting device(160) which selects a series of materials to dock from the database.

Description

System and Method for Searching Materials Interfacing with Proteins Based on Interfaceome and Recording Medium Therefor}

1 is a block diagram of a search system according to an embodiment of the present invention;

2 is a flowchart illustrating a method for searching for an interactive substance according to the present invention;

3 is a block diagram of a search system according to another embodiment of the present invention;

Figure 4 illustrates the process of searching for a substance that interacts with Bak protein by a search method of the present invention.

Figure 5 illustrates the process of searching for a substance that interacts with Bak protein by another search method of the present invention.

<Description of the symbols for the main parts of the drawings>

100: search system 110: control unit

120: database 122: protein database

124: Interfacial Database 126: Compound Database

130: I / O interface 140: interactive tetrahedral extraction device

142: three-dimensional structure generation unit 144: surface structure extraction unit

146: interactive face matching unit 150: interactive material extraction device

160: lead material sorting device 170: docking energy calculation device

172: docking unit 174: energy calculation unit

180: storage means 190: communication network interface

200: personal computer 300: information providing server

310: control unit 320: database

330: network interface 400: the Internet

The present invention relates to a system, a method and a recording medium for searching a substance interacting with a protein. More particularly, the present invention relates to a system, a method and a recording medium for searching a substance interacting with a protein on the basis of an interaction cube. .

Proteins are the smallest functional unit of a cell, and biosignal transmission occurs through the interaction of proteins. In particular, protein interactions play a key role in system biology, an area that is currently in the spotlight. As a result, many countries around the world are putting a lot of effort into researching protein interactions. The current technology of each country is as follows.

Japan's Ito Group released its entire protein network of budding yeast in 2000, and Fields Group of the United States also published its entire protein network of budding yeast in 2001. In addition, venture firm Cellzome announced the protein network of germinating yeast using the TAP / MA technique in 2002, and NDS proteomics of Canada announced the protein network of germinating yeast using MS technique. . In 2003, CuraGen, a venture company, also announced a protein network for fruit flies using the Y2H technique, and this year, the Vidal group of the United States used the Y2H technique to build a protein network for C. elegans. Announced.

However, experimental techniques such as Y2H and TAP / MS, which are used to confirm protein interaction, require a lot of cost and time to identify protein-level protein networks, and have the disadvantage of repeating the same experiment for each species. Bioinformatics approaches have been attempted to overcome these shortcomings, and methods such as gene fusion and phylogenetic profiles have been used. The bioinformatics method that has been carried out to date has the advantage of being able to search in large quantities and at high speeds, but it is difficult to apply to eukaryotic organisms such as humans and rats, and there is a problem of verifying accuracy.

On the other hand, the treatment of lead compounds in drug development can be divided into two stages. The first is Drug Lead Identification in the Chemical Library, and the second is Drug Lead Optimization. In the process of finding drug candidates, the development of high-through screening (HTS) method has recently been prominent. In particular, a compound library is generated by the method of diversity oriented chemical synthesis (DOS) and a large amount of compound using the HTS technique. Random screening method is in the spotlight.

This DOS, HTS technique makes it possible to screen millions of compounds per day for a given drug target protein. However, random screening for new medicinal proteins is very small, with a hit ratio of one hundred thousand as the lead relative to the number of compounds in the experiment. In addition, because of the exponential growth of potential pharmacological proteins due to the development of genomics, the random screening of all medicinal proteins through experiments is inefficient in terms of cost and time.

Accordingly, the present inventors have constructed a database including information on the interacting polyhedron between the protein and other objects in order to search for a substance that interacts with the protein more accurately and quickly, and uses the same to search for a substance that interacts with the protein. A system, method and recording medium were developed.

The present invention is to search for a substance that interacts with the protein based on the interacting polyhedron.

In the present invention, “interactive icosahedron” refers to a group of atoms contacting among atoms constituting the first analyte (protein, protein domain or compound) and atoms constituting the second analyte (protein, protein domain or compound). It is defined by the Euclidean distance method, geometric diagram (eg, Voronoi Diagram) or accessible surface area (Accessible Surface Area). The algorithm is described in detail below.

(i) Euclidean distance method: Each atom constituting the first analyte is selected in this manner by checking whether or not interacting according to the distance with the atoms constituting the second analyte. When atoms are collected, they form an interaction surface.

(ii) geometric diagram: a point corresponding to half of the distance between atoms of each atom constituting the second analyte for each atom constituting the first analyte, which is connected to the first analyte by connecting the points; Interaction planes between the second analytes can be formed.

(iii) Approach mask algorithm: Atoms are selected for contacting the water molecules when the first analyte and the second analyte are separated, and then atoms that contact the water molecules when they are bound. A group of atoms selected from the former but not selected from the latter constitutes an interaction plane between the first analyte and the second analyte.

A more detailed description of “interactive icosahedron” can be referred to from Korean Patent Application No. 2005-0121684, filed December 12, 2005 by the applicant.

The present invention can search for a substance that interacts with any protein using the system and method described below and the recording medium therefor based on the above-described interacting polyhedron.

One aspect of the invention is a control unit; A database that stores information about proteins, information about interacting polyhedrons, and information about compounds; I / O interface; As the amino acid sequence of the protein to be searched is input, a three-dimensional structure of the protein is generated by referring to a database, a surface structure is extracted from the protein, and the surface structure and each of the interacting polyhedrons stored in the database are matched to a specified value or more. An interfacial extraction apparatus for extracting an interfacial surface of the protein into an interfacial surface of the protein; An interaction material extraction device for extracting a material having an interaction face corresponding to the interaction face of the protein to be searched from the database; And / or a docking energy calculation device for docking a material selected from the interacting surface of the protein to be searched and the database and calculating energy at docking; And it provides a search system for a substance that interacts with the protein based on the interacting surface is configured to include a storage means.

On the premise that the search system according to the present invention includes a docking energy calculation device, a series of substances to be docked from a database that docks a selected material from the database and the surface of the interacting polyhedron of the protein to be searched and calculates the energy at the time of docking It is preferred to further comprise a lead material sorting device for sorting.

Another aspect of the invention comprises the steps of inputting the amino acid sequence of the protein to be searched; Generating a three-dimensional structure of the protein; Extracting a surface structure from the generated three-dimensional structure; Matching the surface structure with each of the interacting cubes stored in the database; Extracting the interacting polyhedron of the protein from the interacting polyhedron matching the specified value or more; Extracting a substance having an interaction cube corresponding to the interaction cube of the protein to be searched from the database; And / or docking a material selected from the database and the interacting surface of the protein to be searched and calculating the energy at docking to select a material that docks below a specified energy. Provide a method of searching for a substance.

On the premise that the search method according to the present invention includes the step of docking a selected substance from the interacting surface of the protein to be searched and the database, calculating the energy at the time of docking, and selecting a substance that docks below a specified energy. Preferably, the method further comprises the step of selecting a series of compounds to be docked from a database.

Another aspect of the present invention provides a function of generating a three-dimensional structure with reference to a database as an amino acid sequence of a search target protein is inputted; Extracting a surface structure from the generated three-dimensional structure; Matching the surface structure with each of the interacting cubes stored in the database; Extracting the interacting polyhedron of the protein from the interacting polyhedron matching the specified value or more; Extracting a substance having an interacting body corresponding to the interacting body of the protein to be searched from the database; And / or a computer program for sequentially executing the function of docking a selected substance from the interacting surface of the protein to be searched and the database, calculating the energy at the docking time, and selecting a substance that docks below a specified energy. Provides a record medium that can be.

On the premise that the recording medium according to the present invention includes a function of docking a material selected from an interacting surface of a protein to be searched and a database, and calculating a energy at docking to select a material that docks below a specified energy. Prior to this it is desirable to further perform the function of selecting a series of compounds to be docked from the database.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is a block diagram of a search system according to an embodiment of the present invention.

As shown, the interacting substance search system 100 based on the interacting surface is a control unit 110 that controls the overall operation such as data signal and control signal transmission and reception, the amino acid sequence of the protein and the corresponding three-dimensional structure An input / output device such as a database 120, a monitor, a keyboard, a mouse, and the like, which stores information on information about an object, a structure, and properties of the compound, and information on the object and the object. I / O interface 130 for connection between the interactor search system 100 and the amino acid sequence of the protein to be searched is input through the I / O interface 130. The three-dimensional structure of the protein is generated by reference, and the surface structure is extracted and displayed therefrom. An interactive polyhedron extracting apparatus 140 for extracting an interactive polyhedron matching each of the loaded interactive polyhedrons by a specified value or more, into an interactive polyhedron of the protein; Interactive material extraction device 150 for selecting a substance from the database, a leading material screening device 160 for selecting a series of materials to be docked from the database, a material selected from the database and the interacting surface of the protein to be searched (e.g., Leading material) and information necessary for the operation of the docking energy calculation device 170 and the interactive substance search system 100 that calculates the energy at the time of docking, information on the interacting polyhedron of the protein to be searched, the interacting polyhedron Storage means 180 for storing information about a material having an interacting surface corresponding to It is configured.

In this case, when a user inputs an amino acid sequence of a protein to be searched, a three-dimensional structure of the protein is generated by referring to an amino acid sequence of a known protein and a corresponding three-dimensional structure, and a protein to be searched by referring to a known interaction polyhedron. After extracting the interacting octahedron of the substance to search for interacting with the interacting (eg known compound). To this end, the database 120 applied in the present invention is a protein DB 122, the interacting octahedra and the interaction hexahedral are formed between any object that stores information about the amino acid sequence of the protein and the corresponding three-dimensional structure, etc. It is implemented to include a compound DB 126, which stores information on the interaction, etc., which is stored in the tetrahedron DB 124, and the compound name, structure and properties. As the interacting surface DB, an interacting surface DB constructed by the technology disclosed in Korean Patent Application No. 2005-0121684 filed by the applicant on December 12, 2005 may be used.

In addition, the interactive icosahedral extraction apparatus 140 includes a three-dimensional structure generator 142, a surface structure extractor 144, and an interactive icosahesis matching unit 146. When the amino acid sequence of the search target protein is input through the I / O interface 130, the 3D structure generating unit 142 inquires the database 120 under the control of the controller 110 to determine the amino acid most similar to the amino acid sequence. After extracting the protein having the sequence, the three-dimensional structure of the protein previously extracted based on the amino acid sequence of the protein to be searched is appropriately modified to generate the three-dimensional structure of the protein to be searched.

When the three-dimensional structure of the protein to be searched is generated, the surface structure extractor 144 extracts only the surface structure from the three-dimensional structure. The surface structure extracting unit 144 is necessary because the surface of the protein is substantially involved in the interaction with the object. In one embodiment, the surface structure extraction unit 144 may extract only the surface structure from the three-dimensional structure of the protein to be searched using an access mask algorithm. The algorithm calculates the area in contact with water for each amino acid by rolling water on a three-dimensional structure of the protein, and experimentally obtains the maximum area that the amino acid can contact with water. Extracted with amino acids present on the surface.

When the surface structure is extracted from the three-dimensional structure of the protein to be searched, the interactive facet matching unit 146 individually matches all the surface facets stored in the database 120 with the surface structure under the control of the controller 110. Then, the interacting polyhedron matching the value specified by the user or more is extracted as the interacting polyhedron of the searched protein. As an aspect, the matching unit 146 may individually match the surface structure extracted from the three-dimensional structure of the protein to be searched and all the interacting cubes stored in the database 120 using a structure comparison algorithm. The structure comparison algorithm transforms and rotates the tertiary structure corresponding to the significant alignment result after the alignment of the secondary sequences of the two matching objects. By value the results of the structure comparison are presented. Among the obtained values, the interacting polyhedron matching the value specified by the user or more is extracted as the interacting polyhedron of the target protein.

In this way, when the interacting polyhedron of the protein to be searched is extracted, the interacting substance extraction apparatus 150 extracts a material having the interacting polyhedron corresponding to the interacting polyhedron stored in the database under the control of the controller 110 and The result is output through the I / O interface 130. As described above, since the database 120 of the present invention holds not only information about interacting cubes but also information on which objects the interacting cubes are formed between, once the interacting cubes of the protein to be searched are extracted, It is possible to extract substances that interact with the protein of interest.

On the other hand, it is preferred that the search system of the present invention further includes a lead material sorting device 160 on the premise that the docking energy calculation device 170 to be described later. The lead material sorting device 160 is used in the search system according to the present invention when the docking energy calculation device 170 wants to dock only materials meeting specific conditions among the interacting polyhedron of the searched protein and the material stored in the database. It is preferred to be introduced. The lead substance selection device 160 selects a series of substances (ie, lead substances) to be docked with the interacting surface of the protein to be searched from the substances stored in the database under the control of the controller 110. The lead material is determined by conditions arbitrarily designated by the user, and may be, for example, a material having a specific molecular weight or more, a material having a certain moiety, or a material having a specific chemical bond.

In addition, the docking energy calculation device 170 includes a docking unit 172 and the energy calculation unit 173. The interacting surface of the protein to be searched is extracted by the interacting surface extracting apparatus 140, and a predetermined substance is selected from a database under the control of the controller 110, or the screening system of the present invention is selected as the leading substance. When the lead material to be docked is selected from the database by the lead material sorting device 160, the docking unit 172 is controlled by the control unit 110 and the interacting surface of the protein to be searched Individually dock the selected material or lead material from the database.

The energy calculation unit 174 calculates the energy at the time of docking with the interacting surface for each material or lead material selected from the database, and outputs the value through the I / O interface 130. As an aspect, the energy calculation unit 174 may calculate the exact position and direction by using Equation 1 below when a predetermined material or lead material selected from the database docks with the interacting surface.

E _bind = E _vdw + E _elec

Docking energy ( E _bind ) can be divided into a function of distance ( E _vdw ) and a function of electrical energy ( E _elec ). Here, the distance function is expressed as statistical van der Waals energy, which represents the attractive force and repulsive force by the distance between the interacting atoms and the leading material atoms. The electrostatic energy function is a representation of the electrostatic energy between the docking atoms and represents the attractive force and repulsive force between the positive and negative charges.

2 is a flowchart illustrating a method for searching for an interactive substance according to the present invention.

First, a user inputs an amino acid sequence of a search target protein through an input device (S110). When the amino acid sequence of the protein is input, for example, a keyboard or the like may be directly inputted, or the amino acid sequence of the protein to be searched may be selected and input from the amino acid sequence list of the protein stored in the database 120.

As the amino acid sequence of the search target protein is input, the 3D structure generator 142 searches the database 120 to select a protein having an amino acid sequence most similar to the amino acid sequence of the search target protein, and the amino acid of the search target protein. By appropriately modifying the three-dimensional structure of the protein selected previously with reference to the sequence to generate a three-dimensional structure of the target protein (S120).

When the three-dimensional structure of the search target protein is generated, the surface structure extractor 144 extracts a surface structure substantially involved in the interaction between the search target protein and the target object from the three-dimensional structure of the search target protein (S130).

When the surface structure is extracted from the three-dimensional structure of the protein to be searched, the interactive facet matching unit 146 individually matches the surface of the protein to be searched and the interacting facets stored in the database (S140), and the value specified or more. By matching the matching polyhedron is extracted as the interaction polyhedron of the target protein (S150).

In this way, when the interacting polyhedron of the protein to be searched is extracted, the materials having the interacting polyhedron corresponding to the interacting polyhedron are selected with reference to the database 120 (S160). Since the database 120 of the present invention retains not only information about the interacting polyhedron but also information on which objects the interacthedron is formed between, once the interacting polyhedron of the protein to be searched is extracted, It is possible to extract the interacting substance.

On the other hand, on the premise that the search method of the present invention includes the steps (S180-S200) to be described later, the lead material screening device 160 is docked on the interacting surface of the previously searched protein from the substances stored in the database It is preferable to include a step of selecting a series of materials to be selected according to a user specified criteria (S170). The step (S170) is introduced to the search method according to the present invention in the case that the next step (S180 and S190) to dock only those substances that meet a specific condition among the material of the interacting polyhedron and the database stored in the database to be searched It is preferable.

In this way, when the interacting surface of the protein to be searched is first extracted, and a predetermined material stored in the database is selected, or a lead material is selected from the lead material extracting device 160, the docking energy calculation device 170 determines the The predetermined material or the leading material selected from the interacting surface and the database are individually docked (S180), and an energy value is calculated at docking (S190). Subsequently, a predetermined substance or a leading substance selected from a database docked below a specified energy value by the user is selected as an interacting substance (S200), because such a substance is expected to interact with a protein to be searched.

The interactive substance search system described above has a difficulty in reflecting this in real time when the database 120 is changed because the database 120 is independently established for each system. Therefore, if the database 120 is managed in a specific server system, and the database 120 is shared through a communication network such as the Internet, even if the database 120 is changed, it is always possible to search for the interactive substance using the latest data. It is expected to be. The interactive substance search system for this is shown in FIG. 3.

3 is a block diagram of another embodiment of a first aspect of a search system according to the present invention.

The interactive substance analyzing system according to the present embodiment includes a personal computer equipped with an interactive tetrahedral extraction device 140, an interactive substance extraction device 150, a leading material sorting device 160, and a docking energy calculation device 170. 200, the personal computer 200 and the information providing server 300 connected through a communication network such as the Internet 400.

The personal computer 200 connects an input / output device (not shown) such as a control unit 110, a monitor, a keyboard, a mouse, and the like to control the overall operation such as transmitting and receiving data signals and control signals, and the interactive substance search system 100. As the amino acid sequence of the I / O interface 130 for the protein to be searched is input through the I / O interface 130, the three-dimensional structure of the protein is generated with reference to the database 320, and the surface structure is derived therefrom. After extracting and representing the surface of the surface and the corresponding interaction cubes stored in the database to match the interaction polyhedron to extract more than a specified value to the interaction cube of the search target protein 140 and the extracted Interaction material extraction device 150 for extracting a protein having an interacting surface corresponding to the interacting surface from the database , A lead material selection device 160 for selecting a series of materials to be docked from a database, a docking energy for docking a selected material (eg, lead material) from a database and interacting facets of a protein to be searched and docking Stores information necessary for the operation of the calculation device 170, the interactive substance search system 100, information on the interacting polyhedron of the target protein, information on the material having the interacting polyhedron corresponding to the interacting polyhedron, etc. And a communication network interface 190 for connecting to the information providing server 300 through the storage means 180 and the Internet 400.

Here, the interactive icosahedral extraction apparatus 140 includes a three-dimensional structure generator 142, a surface structure extractor 144, and an interactive icosahesis matching unit 146, and the function and operation of each processing unit are illustrated in FIG. 1. Since it is similar to that described in the detailed description thereof will be omitted. In the case of the interactive substance extracting device 150, the functions and operations are similar to those described above, and thus the description thereof will be omitted.

Meanwhile, the lead material extracting device 160 is introduced under the premise of including the docking energy calculating device 170, and the docking energy calculating device 170 includes a docking unit 172 and an energy calculating unit 174. Since the functions and operations of the devices and the processing units are similar to those described in FIG. 1, detailed descriptions thereof will be omitted.

Meanwhile, the information providing server 300 includes a controller 310, a communication network interface 330, and a database 320. The database 320 includes a protein DB 122 in which amino acid sequence information of a protein and corresponding three-dimensional structure information are stored, and an interaction polyhedron DB in which information about an interaction polyhedron and an object of the interaction polyhedron is formed is stored. 124 and information about the name, structure, and properties of the compound, and the like, including the stored compound DB 126.

In this embodiment, since the information providing server 300 centrally manages the amino acid sequence, the three-dimensional structure, and the information about the interacting surface of the protein that is the basis of the interaction analysis material, new proteins and interacting surfaces are discovered. In this case, it is easy to update the database 320 collectively, and the user of each personal computer 200 may use the latest three-dimensional information.

In addition, the interactive icosahedral extraction device 140, the interaction material extraction device 150, the lead material screening device 160, the docking energy calculation device 170 is composed of an independent device connected to the personal computer 200 It is also possible, but it is also possible to configure one software that can perform this function. In the case of producing software having the functions of the interfacial extraction device 140, the interaction material extraction device 150, the leading material sorting device 160, the docking energy calculation device 170, the information providing server 300 It can be downloaded to the user who requests it, and the user can install it on the personal computer 200 and use it for searching for interactive substances, or it can be produced in a form stored in all possible recording media such as floppy disk, CD, DVD, and the like. Do.

Figure 4 shows the process and results of searching for substances that interact with Bak protein according to the search method of the present invention.

As the amino acid sequence of the Bak protein shown in FIG. 4A is input, a database is searched to find a protein having an amino acid sequence most similar to the amino acid sequence, and the three-dimensional structure of the protein is modified with reference to the amino acid sequence of the Bak protein to Bak. The three-dimensional structure of the protein was generated (see FIG. 4B). Only the surface structure was extracted from the three-dimensional structure of the Bak protein thus produced, as shown in FIG. 4C. Subsequently, the interaction cubes stored in the database were individually matched to the surface structure of the Bak protein to select the interaction cubes matching the specified value or more. The icosahedron lfnv_dlfnval_dlfnvbl_A was eventually extracted into the icosahedron of Bak protein (see FIG. 4D), and although not shown in the figure, all substances with lfnv_dlfnval_dlfnvbl_B corresponding to the icosahedron could be predicted to interact with Bak protein.

Figure 5 shows the process and results of searching for compounds that interact with Bak protein according to the search method of the present invention.

Several lead materials were docked in the interacting polyhedron lfnv_dlfnval_dlfnvbl_A shown in FIG. 4D (see FIG. 5A), and the energy at the time of docking for each lead material was calculated and shown graphically (see FIG. 5B). The graph shows that the Y-axis is related to energy, and the leading material docked with the energy value of -32 in the upper right corner of the graph is the compound that interacts most strongly and strongly with the interacting surface.

A system and method for screening a substance interacting with a protein based on an icosahedron according to the present invention, and using a recording medium therefor, for a molecular level prediction of a protein interaction and a novel screening method for a new drug leader Can be.

Claims (9)

Control unit; A database that stores information about proteins, information about interacting polyhedrons, and information about compounds; I / O interface; As the amino acid sequence of the protein to be searched is input, a three-dimensional structure of the protein is generated by referring to a database, a surface structure is extracted from the protein, and the surface structure and each of the interacting polyhedrons stored in the database are matched to a specified value or more. An interfacial extraction apparatus for extracting an interfacial surface of the protein into an interfacial surface of the protein; An interaction material extraction device for extracting a material having an interaction face corresponding to the interaction face of the protein to be searched from the database; And A docking energy calculation device for docking a material selected from an interacting polyhedron and a database of a search target protein and calculating energy at docking; And Apparatus for retrieving a substance interacting with a protein based on the interacting surface, including a storage means. The method of claim 1, Searching apparatus for interacting with the protein based on the interacting surface, characterized in that it further comprises a leader screening device for selecting a series of materials to be docked from the database. The method of claim 1, The apparatus for extracting an interactive polyhedron extracts a surface structure from a three-dimensional structure of a protein to be searched using an access mask algorithm. The method of claim 1, The apparatus for extracting an interacting polyhedron extracts the interacting polyhedron of a protein to be searched using a structure comparison algorithm. The method of claim 1, Docking energy calculation device is the following equation [1] E _bind = E _vdw + E _elec Searching device, characterized in that for calculating the docking energy between the interacting surface of the protein to be searched and the material selected from the database using.  Inputting an amino acid sequence of a protein to be searched for; Generating a three-dimensional structure of the protein; Extracting a surface structure from the generated three-dimensional structure; Matching the surface structure with each of the interacting cubes stored in the database; Extracting the interacting polyhedron of the protein from the interacting polyhedron matching the specified value or more; Extracting a substance having an interaction cube corresponding to the interaction cube of the protein to be searched from the database; And Search for a substance that interacts with a protein based on an icosahedron, including docking the selected substance from the database and the database of the protein of interest, and calculating the energy at docking to select a substance that docks below the specified energy Way. The method of claim 6, Docking a selected material from the interacting polyhedron and database of the protein to be searched, calculating the energy at docking, and selecting a series of compounds to be docked from the database prior to selecting the material to dock below a specified energy. Search method comprising the. A function of generating a three-dimensional structure by referring to a database as an amino acid sequence of a search target protein is input; Extracting a surface structure from the generated three-dimensional structure; Matching the surface structure with each of the interacting cubes stored in the database; Extracting the interacting polyhedron of the protein from the interacting polyhedron matching the specified value or more; Extracting a substance having an interacting body corresponding to the interacting body of the protein to be searched from the database; And A computer-readable recording medium in which a program for sequentially performing a function of docking a selected substance from a database and a database of a target protein to be searched, calculating an energy at docking, and selecting a substance that docks below a specified energy is recorded. . The method of claim 8, In addition to the ability to dock a selected substance from the interacting polyhedron and database of the protein to be searched, calculate the energy at the time of docking, and select a substance that docks below the specified energy. A recording medium, characterized in that for executing.

Images