JP-7855840-B2 - Initial structure generation apparatus, initial structure generation method, and initial structure generation program

Inventors

• 谷田 義明

Assignees

• 富士通株式会社

Dates

Publication Date

20260511

Application Date

20210927

Claims (10)

1. A generation unit that identifies the Cα atom of each of several amino acid residues, arranges each of the identified Cα atoms along a circumference of a circle with a radius calculated based on the distance between adjacent Cα atoms , and then adds the main chain and side chains of the several amino acid residues to generate a model representing a cyclic peptide molecule. An initial structure generation apparatus having a search instruction unit that instructs a search unit to search for a stable structure of the cyclic peptide molecule using the generated model as the initial structure of the cyclic peptide molecule.
2. The initial structure generating apparatus according to claim 1, wherein the generating unit arranges each of the Cα atoms at equal intervals on the circumference.
3. The generating unit arranges n Cα atoms at coordinates = [rsin(n-1) θx , rcos(n-1) θx ] such that the distance between adjacent Cα atoms is a (where r = (a/2) × [sin(π/n)] - 1 , θx = x × 2π/n, x = an integer from 1 to n), the initial structure generating apparatus according to claim 1.
4. The initial structure generation apparatus according to claim 1, wherein the generation unit generates a model representing the cyclic peptide molecule by relaxing the structure after addition.
5. The initial structure generation apparatus according to claim 4, wherein the generation unit relaxes the structure after addition while the Cα atom is fixed.
6. The initial structure generating apparatus according to claim 4, wherein the generating unit relaxes the structure after addition, including the Cα atom.
7. The initial structure generation apparatus according to claim 1, further comprising a calculation unit that calculates the dihedral angle distribution based on the dihedral angle of the backbone when a stable structure is searched based on the instructions from the search instruction unit.
8. The initial structure generation apparatus according to claim 1, wherein the search unit searches for a stable structure using the generated model as the initial structure of the cyclic peptide molecule by an extended ensemble method.
9. A model representing a cyclic peptide molecule is generated by identifying the Cα atoms of each of several amino acid residues, arranging each of the identified Cα atoms along a circumference with a radius calculated based on a specified distance between adjacent Cα atoms , and then adding the main chain and side chains of the several amino acid residues. The generated model is used as the initial structure of the cyclic peptide molecule, and the search unit is instructed to search for a stable structure of the cyclic peptide molecule. A method for generating an initial structure in which a computer performs processing.
10. A model representing a cyclic peptide molecule is generated by identifying the Cα atoms of each of several amino acid residues, arranging each of the identified Cα atoms along a circumference with a radius calculated based on a specified distance between adjacent Cα atoms , and then adding the main chain and side chains of the several amino acid residues. The generated model is used as the initial structure of the cyclic peptide molecule, and the search unit is instructed to search for a stable structure of the cyclic peptide molecule. An initial structure generation program for enabling a computer to perform a process.

Description

This invention relates to an initial structure generation apparatus, an initial structure generation method, and an initial structure generation program. In recent years, drug discovery has seen increased interest in the development of medium-sized molecules (molecular weight 500-3000) with fewer side effects, and research methods for finding stable structures of these medium-sized molecules are being developed. In particular, cyclic peptide molecules are attracting considerable attention because cyclization significantly reduces entropy, allowing for the creation of compounds with high binding activity. Japanese Patent Publication No. 2010-159218Japanese Patent Publication No. 2020-091518U.S. Patent Application Publication No. 2018/0260517 F. Jiang and H. Geng, "Computational Methods for Studying Conformational Behaviors of Cyclic Peptides", 2019 This figure shows an example of the system configuration, terminal device, and server device functional configuration of a stable structure search system.This figure shows an example of the hardware configuration of terminal and server devices.This figure shows an example of the functional configuration of the cyclic peptide molecule generation section.This figure shows a specific example of processing the Cα atom arrangement region.This figure shows specific examples of processing for the added portion and the structural relaxation portion.This is a diagram to explain the dihedral angle of the backbone.Figure 1 shows an example of a dihedral angle distribution diagram.The second figure shows an example of a dihedral angle distribution diagram.This is a flowchart showing the flow of the stable structure search process. The following descriptions of each embodiment will be made with reference to the attached drawings. In this specification and the drawings, components having substantially the same functional configuration are denoted by the same reference numerals, thus omitting redundant descriptions. [First Embodiment] <System configuration of the stable structure search system, and functional configuration of terminal and server devices> First, the system configuration of the stable structure search system according to the first embodiment and the functional configurations of the terminal device and server device constituting the stable structure search system will be described. Figure 1 is a diagram showing an example of the system configuration, terminal device and server device of the stable structure search system. The stable structure search system 100 is a system for searching for stable structures of medium-sized molecules, and in particular, a system for searching for stable structures of cyclic peptide molecules having multiple amino acid residue sequences. As shown in Figure 1, the stable structure search system 100 includes a terminal device 110, which is an example of an initial structure generation device, and a server device 120. The terminal device 110 has a search program installed. When this program is executed, the terminal device 110 functions as an amino acid residue sequence acquisition unit 111, a cyclic peptide molecule generation unit 112, a dihedral angle distribution calculation unit 113, and a stable structure output unit 114. The amino acid residue sequence acquisition unit 111 is an example of an acquisition unit. When a user of the stable structure search system 100 inputs multiple amino acid residue sequences constituting a cyclic peptide molecule to be searched, the system acquires these sequences. Furthermore, the amino acid residue sequence acquisition unit 111 acquires the parameters (distance "a," described later) used to generate the initial structure of the cyclic peptide molecule to be searched, when the user of the stable structure search system 100 inputs these parameters. The cyclic peptide molecule generation unit 112 is an example of a generation unit. Based on multiple amino acid residue sequences obtained by the amino acid residue sequence acquisition unit 111, it generates a model representing a cyclic peptide molecule under the obtained parameters, which serves as the initial structure of the cyclic peptide molecule. Furthermore, the cyclic peptide molecule generation unit 112 is an example of a search instruction unit. By transmitting information indicating the initial structure of the generated cyclic peptide molecule to the server device 120, it instructs the server device 120 to search for a stable structure based on this initial structure. Details of the method for generating the initial structure of a cyclic peptide molecule by the cyclic peptide molecule generation unit 112 will be described later. The dihedral angle distribution calculation unit 113 is an example of a calculation unit. In response to the transmission of information indicating the initial structure of the cyclic peptide molecule by the cyclic peptide molecule generation unit 112, it acquires information indicating the dihedral angles of the