US-20260128135-A1 - EVOLUTIONARY ALGORITHM FOR SEARCHING FOR A CHEMICAL STRUCTURE HAVING A TARGET PHYSICAL PROPERTY THAT MAINTAINS STRCUTURAL DIVERSITY AMONG CANDIDATES

US20260128135A1US 20260128135 A1US20260128135 A1US 20260128135A1US-20260128135-A1

Abstract

An object of the present invention is to provide a method for searching a compound, a program for searching a compound, a recording medium, and a device for searching a compound, which are capable of efficiently searching a structure of a compound. In the method for searching a compound according to the first aspect, because of performing a first adoption process to determine based on whether or not a physical property value of a candidate structure approaches a target value of a physical property value due to a change in chemical structure, in a case where the candidate structure is not adopted as a result of the first adoption process, performing a second adoption process to determine based on whether or not a structural diversity increases, and in a case where the candidate structure is not adopted as a result of the first adoption process and the second adoption process, performing a rejection process to reject the change in chemical structure and return to the chemical structure before the change, it is possible to improve the structural diversity to promote escape from local minimum, and efficiently search for the structure of the compound having a desired physical property value (target value).

Inventors

Jun NAKABAYASHI

Assignees

FUJIFILM CORPORATION

Dates

Publication Date: 20260507
Application Date: 20260105
Priority Date: 20180914

Claims (14)

1 . A device for searching a compound, comprising a processor and a non-transitory and tangible memory, wherein the processor is configured to perform, by referring the memory: inputting a chemical structure of one or more compounds, one or more physical property values according to the chemical structure, and a target value of the physical property values; acquiring a candidate structure by changing the chemical structure; calculating the physical property value of the candidate structure; adopting or rejecting the candidate structure, in which a first adoption process is performed to determine whether to or not to adopt the candidate structure based on whether or not the physical property value of the candidate structure approaches the target value of the physical property value due to the change in chemical structure, in a case where the candidate structure is not adopted by the first adoption process, a second adoption process is performed to determine whether to or not to adopt the candidate structure based on whether or not a structural diversity of a structural group composed of the chemical structure and the candidate structure increases due to the change in chemical structure, and in a case where the candidate structure is not adopted by the first adoption process and the second adoption process, a rejection process is performed to reject the change in chemical structure and return to the chemical structure before the change; and controlling to repeat the inputting, the acquiring of the candidate structure, the calculating of the physical property value, and the adopting-or-rejecting of the candidate structure, until a termination condition is satisfied.
2 . A device for searching a compound, comprising a processor and a non-transitory and tangible memory, wherein the processor is configured to perform, by referring the memory: inputting a chemical structure of one or more compounds, one or more physical property values according to the chemical structure, and a target value of the physical property values; acquiring a candidate structure by changing the chemical structure; calculating the physical property value of the candidate structure; adopting or rejecting the candidate structure, in which a second adoption process is performed to determine whether to or not to adopt the candidate structure based on whether or not a structural diversity of a structural group composed of the chemical structure and the candidate structure increases due to the change in chemical structure, in a case where the candidate structure is not adopted by the second adoption process, a first adoption process is performed to determine whether to or not to adopt the candidate structure based on whether or not the physical property value of the candidate structure approaches the target value of the physical property value due to the change in chemical structure, and in a case where the candidate structure is not adopted by the first adoption process and the second adoption process, a rejection process is performed to reject the change in chemical structure and return to the chemical structure before the change; and controlling to repeat the inputting, the acquiring of the candidate structure, the calculating of the physical property value, and the adopting-or-rejecting of the candidate structure, until a termination condition is satisfied.
3 . A device for searching a compound, comprising a processor and a non-transitory and tangible memory, wherein the processor is configured to perform, by referring the memory: inputting a chemical structure of one or more compounds, one or more physical property values according to the chemical structure, and a target value of the physical property values; acquiring a candidate structure by changing the chemical structure; calculating the physical property value of the candidate structure; adopting or rejecting the candidate structure, in which a first calculation process and a second calculation process are simultaneously performed, wherein the first calculation process is for calculating a first adoption probability of adopting the candidate structure based on whether or not the physical property value of the candidate structure approaches the target value of the physical property value due to the change in chemical structure, the second calculation process is for calculating a second adoption probability of adopting the candidate structure based on whether or not a structural diversity of a structural group composed of the chemical structure and the candidate structure increases due to the change in chemical structure, the candidate structure is adopted based on the first adoption probability and the second adoption probability, and the change in chemical structure is rejected to return to the chemical structure before the change in a case where the candidate structure is not adopted; and controlling to repeat the inputting, the acquiring of the candidate structure, the calculating of the physical property value, and the adopting-or-rejecting of the candidate structure, until a termination condition is satisfied.
4 . The device for searching a compound according to claim 1 , wherein the processor is configured to perform: as the first adoption process in the adopting-or-rejecting of the candidate structure, in a case where an absolute value of a difference between the physical property value of the candidate structure and the target value of the physical property value is equal to or less than an absolute value of a difference between the physical property value of the chemical structure and the target value of the physical property value, adopting the candidate structure, and in a case where the absolute value of the difference between the physical property value of the candidate structure and the target value of the physical property value is more than the absolute value of the difference between the physical property value of the chemical structure and the target value of the physical property value, calculating a first adoption probability from a first function based on the difference between the physical property value of the candidate structure and the target value of the physical property value and adopting the candidate structure with the first adoption probability.
5 . The device for searching a compound according to claim 2 , wherein the processor is configured to perform: as the first adoption in the adopting-or-rejecting of the candidate structure, in a case where an absolute value of a difference between the physical property value of the candidate structure and the target value of the physical property value is equal to or less than an absolute value of a difference between the physical property value of the chemical structure and the target value of the physical property value, adopting the candidate structure is performed, and in a case where the absolute value of the difference between the physical property value of the candidate structure and the target value of the physical property value is more than the absolute value of the difference between the physical property value of the chemical structure and the target value of the physical property value, calculating a first adoption probability from a first function based on the difference between the physical property value of the candidate structure and the target value of the physical property value and adopting the candidate structure with the first adoption probability.
6 . The device for searching a compound according to claim 1 , wherein the processor is configured to perform: as the second adoption process in the adopting-or-rejecting of the candidate structure, calculating an increase or decrease amount in the structural diversity of the structural group, calculating a second adoption probability from a second function based on the increase or decrease amount, and adopting the candidate structure with the second adoption probability.
7 . The device for searching a compound according to claim 2 , wherein the processor is configured to perform: as the second adoption process in the adopting-or-rejecting of the candidate structure, calculating an increase or decrease amount in the structural diversity of the structural group, calculating a second adoption probability from a second function based on the increase or decrease amount, and adopting the candidate structure with the second adoption probability is performed.
8 . The device for searching a compound according to claim 3 , wherein the processor is configured to perform: in the adopting-or-rejecting of the candidate structure, in a case where an absolute value of a difference between the physical property value of the candidate structure and the target value of the physical property value is equal to or less than an absolute value of a difference between the physical property value of the chemical structure and the target value of the physical property value, adopting the candidate structure, and in a case where the absolute value of the difference between the physical property value of the candidate structure and the target value of the physical property value is more than the absolute value of the difference between the physical property value of the chemical structure and the target value of the physical property value, calculating the first adoption probability from a first function based on the difference between the physical property value of the candidate structure and the target value of the physical property value, and a process of calculating an increase or decrease amount in the structural diversity of the structural group and calculating the second adoption probability from a second function based on the increase or decrease amount.
9 . The device for searching a compound according to claim 6 , wherein the processor is configured to perform: in the adopting-or-rejecting of the candidate structure, calculating a difference between a structural diversity of a first structural group composed of chemical structures before the change and a structural diversity of a second structural group composed of chemical structures after at least one change, as the increase or decrease amount.
10 . The device for searching a compound according to claim 6 , wherein the processor is configured to perform: in the adopting-or-rejecting of the candidate structure, calculating a difference between a structural diversity of a first structural group including at least a part of structural groups after at least one change and a structural diversity of a second structural group obtained by adding the candidate structure to the first structural group, as the increase or decrease amount.
11 . The device for searching a compound according to claim 4 , wherein the first function is a monotonically decreasing function with respect to a difference between the absolute value of the difference between the physical property value of the candidate structure and the target value of the physical property value, and the absolute value of the difference between the physical property value of the chemical structure and the target value of the physical property value.
12 . The device for searching a compound according to claim 6 , wherein the second function is a monotonically increasing function with respect to the increase or decrease amount in the structural diversity.
13 . The device for searching a compound according to claim 1 , wherein the processor is configured to perform: in the acquiring of the candidate structure, generating an objective structure by adding an atom or an atomic group to the chemical structure or by deleting an atom or an atomic group from the chemical structure, and defining the objective structure as the candidate structure.
14 . The device for searching a compound according to claim 1 , wherein the processor is configured to perform: in the controlling, determining the termination condition is satisfied in a case where the number of times that the chemical structure is changed reaches a specified number of times and/or a case the physical property value of the candidate structure reaches the target value, and terminating the inputting, the acquiring of the candidate structure, the calculating of the physical property value, and the adopting-or-rejecting of the candidate structure.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a Continuation of copending application Ser. No. 17/192,034, filed on Mar. 4, 2021, which is a Continuation of PCT International Application No. PCT/JP2019/036074, filed on Sep. 13, 2019, which claims the benefit under 35 U.S.C. § 119(a) to Patent Application No. 2018-172578, filed in Japan on Sep. 14, 2018, all of which are hereby expressly incorporated by reference into the present application. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for searching a compound, a program for searching a compound, a recording medium, and a device for searching a compound, and particularly relates to a technique for searching a structure of a compound having a desired physical property value. 2. Description of the Related Art In the related art, the search for a structure of a compound having a desired physical property value has been performed mainly by solving a “forward problem” (giving a molecular structure as a cause of the problem and obtaining a physical property value as a result), but with the development of informatics in recent years, studies on a solution method of an “inverse problem” (giving a physical property value and obtaining a molecular structure having the physical property value) are rapidly progressing. For example, “Bayesian molecular design with a chemical language model”, Hisaki Ikebata et al., “searched on Jul. 23, 2018”, internet is known for searching for a structure by solving the inverse problem. The “Bayesian molecular design with a chemical language model”, Hisaki Ikebata et al., “searched on Jul. 23, 2018”, internet discloses that a structure having a physical property value close to the target value is obtained by, giving a target value of physical property value, (1) generating a plurality of initial structures (chemical structures), (2) randomly changing each structure, (3) estimating the physical property value of each structure, and (4) adopting or rejecting the change in structure based on the distance between the physical property value and the target value (in this process, the processes (2) to (4) are repeated). SUMMARY OF THE INVENTION The Inverse Quantitative Structure-Property Relationship (iqspr) disclosed in the “Bayesian molecular design with a chemical language model”, Hisaki Ikebata et al., “searched on Jul. 23, 2018”, internet has a problem that the search efficiency is immediately lowered. For example, FIG. 21 is a diagram showing search results of a compound having a first excitation energy (57.2 kcal/mol) corresponding to a wavelength of 500 nm (mean values of top 100 compounds in each trial calculated by ZINDO using a quantum chemistry calculation software “Gaussian16” is plotted). In the iqspr, as shown in FIG. 21, the search quickly falls into a local minimum (state in which the physical property value moves away from the target value no matter how the structure is minutely changed), which slows the search. The cause of this slow search lies in a structural update algorithm (particulate filter based on Bayesian inference). FIGS. 22A to 22C are conceptual diagrams showing the algorithm of the particulate filter, and in a case where weight is calculated based on the physical property value from an initial state shown in FIG. 22A, a state shown in FIG. 22B is obtained. In a case where sampling with replacement is performed from this state based on the weight (extraction of the same structure is accepted), as shown in FIG. 22C, the structures C and D in which physical property values move away from the target are removed. In addition, FIG. 23 is a table showing an example of the relationship between the initial structural formula of the compound (left column) and the structural formula of the 10th trial (right column), and shows a state in which all the structures are similar as the trials are repeated even though various structures are given in the initial state. As shown in FIGS. 21 to 23, in the structural update based on Bayesian inference, although the physical property value approaches the target value, the diversity of structures for search is reduced, the search falls into the local minimum, and even in a case where the trial is repeated, it is not possible to escape from the local minimum state (it is not possible to reach the final structure). As described above, in the technique in the related art, it is not possible to efficiently search for the structure of the compound. The present invention has been studied in view of such circumstances, and an object of the present invention is to provide a method for searching a compound, a program for searching a compound, a recording medium, and a device for searching a compound, which are capable of efficiently searching a structure of a compound. In order to achieve the above-described object, a method for searching a compound according to a first aspect of the present invention includes: an input step of