Method and apparatus for automated design of chemical synthesis routes

• US 6,571,226 B1
• Filed: 03/10/2000
• Issued: 05/27/2003
• Est. Priority Date: 03/12/1999
• Status: Expired due to Fees

• Current Assignee: Numerate, Inc.
• Original Assignee: PHARMIX CORP. (Numerate, Inc.)
• Inventors: Mydlowec, William J., Yu, Jessen
• Primary Examiner(s): Davis, George B.
• Application Number:
  US09/523,334
• Time in Patent Office: 1,173 Days
• Field of Search: 706/13, 706/12
• US Class Current: 706/13
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: G16C 20/10 Analysis or design of chemical reactions, syntheses or processes

Abstract

Method and apparatus for designing a synthesis route for a target molecule is provided. The method for designing a synthesis route for a target molecule comprises: generating a plurality of individuals, wherein each individual encodes a synthesis route; decoding each individual to produce a synthesis route comprising at least one reactant molecules and at least one reaction; and determining how well the synthesis route satisfies a design goal. A computer readable medium containing instructions for a computer program executable by the computer to perform a method for designing a synthesis route for a target molecule is also provided. The apparatus comprises a parallel computer system for executing instructions of a computer program to perform a method for designing a synthesis route for a target molecule.

Claims

1. A method for designing a synthesis route for a target molecule, comprising:

generating a plurality of individuals, wherein each individual encodes a synthesis route;

decoding each individual to produce a synthesis route comprising at least one reactant molecule and at least one reaction, and

determining whether the synthesis route satisfies a design goal.

2. The method of claim 1, wherein the individual encodes a synthesis route as a program comprising a plurality of instructions which are executed to produce the synthesis route.

3. The method of claim 2, wherein the program conforms to a constrained structure.

4. The method of claim 1, wherein the decoding step comprises retrieving at least one reactant molecule from a data structure of molecules.

5. The method of claim 4, wherein the decoding step further comprises retrieving at least one set of reaction conditions from a data structure of reaction conditions.

6. The method of claim 5, wherein the decoding step further comprises evaluating at least one reaction utilizing the at least one reactant molecule and the at least one set of reaction conditions to output at least one product molecule.

7. The method of claim 6, wherein the evaluation is performed utilizing a computer-based reaction predictor.

8. The method of claim 6, wherein the evaluation is accomplished by physically performing the reaction.

9. The method of claim 1, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a structural similarity between a target molecule and a final product molecule of the synthesis route.

10. The method of claim 9, wherein the step of determining structural similarity comprises comparing the final product molecule and the target molecule utilizing a graph isomorphism algorithm.

11. The method of claim 9, wherein the step of determining structural similarity comprises generating and comparing reduced representations of the final product molecule and the target molecule.

12. The method of claim 11, wherein the reduced representation comprises a bit string and wherein the step of comparing reduced representations utilizes a bit string distance metric.

13. The method of claim 1, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a yield value of the final product molecule.

14. The method of claim 1, further comprising:

performing a selected operation on at least one selected individual to produce a new individual; and

adding the individual produced by the selected operation to the population.

15. The method of claim 14, wherein the step of performing a selected operation comprises performing a crossover operation, the crossover operation comprising:

combining at least one portion from the selected individual and at least one portion from another selected individual to produce a new individual.

16. The method of claim 14, wherein the step of performing a selected operation comprises performing a mutation operation, the mutation operation comprising:

replacing at least one portion of the selected individual with a randomly generated portion to produce a new individual.

17. The method of claim 14, wherein the step of performing a selected operation comprises performing a molecule noise operation comprising:

generating a similarity value;

selecting at least one molecule encoded by the selected individual; and

modifying the selected individual to encode a new molecule based on the similarity value the selected at least one molecule.

18. The method of claim 14, wherein the selected individual is selected based on the determination of how well the synthesis route associated with the individual satisfies the design goal.

19. The method of claim 14, wherein the selected operation is probabilistically chosen from the group of operations consisting of crossover, mutation, molecule noise and copy.

20. The method of claim 1, wherein the steps are performed utilizing a computer system having a plurality of processors.

21. A computer readable medium containing instructions to perform a method comprising:

generating a plurality of individuals, wherein each individual encodes a synthesis route;

decoding each individual to produce a synthesis route comprising at least one reactant molecule and at least one reaction, and

determining whether the synthesis route satisfies a design goal.

22. The computer readable medium of claim 21, wherein the decoding step comprises:

retrieving at least one reactant molecule from a data structure of molecules;

retrieving at least one set of reaction conditions from a data structure of reaction conditions; and

evaluating at least one reaction utilizing the at least one reactant molecule and the at least one set of reaction conditions to output at least one product molecule.

23. The computer readable medium of claim 22, wherein the evaluation is performed utilizing a computer-based reaction predictor.

24. The computer readable medium of claim 21, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a structural similarity between a target molecule and a final product molecule of the synthesis route.

25. The computer readable medium of claim 24, wherein the step of determining structural similarity comprises comparing the final product molecule and the target molecule utilizing a graph isomorphism algorithm.

26. The computer readable medium of claim 24, wherein the step of determining structural similarity comprises generating and comparing reduced representations of the final product molecule and the target molecule.

27. The computer readable medium of claim 21, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a yield value of the final product molecule.

28. The computer readable medium of claim 21, wherein the method further comprises:

performing a selected operation on at least one selected individual to produce a new individual; and

adding the individual produced by the selected operation to the population.

29. The computer readable medium of claim 21, wherein the selected operation is probabilistically chosen from the group of operations consisting of crossover, mutation, molecule noise and copy.

30. A parallel computer system to execute instructions to perform a method for designing a synthesis route comprising the steps of:

generating a plurality of individuals, wherein each individual encodes a synthesis route;

decoding each individual to produce a synthesis route comprising at least one reactant molecule and at least one reaction, and

determining how well the synthesis route satisfies a design goal.

31. The apparatus of claim 30, wherein the decoding step comprises:

retrieving at least one reactant molecule from a data structure of molecules;

retrieving at least one set of reaction conditions from a data structure of reaction conditions; and

evaluating at least one reaction utilizing the at least one reactant molecule and the at least one set of reaction conditions to output at least one product molecule.

32. The apparatus of claim 30, wherein the evaluation is performed utilizing a computer-based reaction predictor.

33. The apparatus of claim 30, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a structural similarity between a target molecule and a final product molecule of the synthesis route.

34. The apparatus of claim 30, wherein the step of determining structural similarity comprises comparing the final product molecule and the target molecule utilizing a graph isomorphism algorithm.

35. The apparatus of claim 30, wherein the step of determining structural similarity comprises generating and comparing reduced representations of the final product molecule and the target molecule.

36. The apparatus of claim 30, wherein the step of determining whether the synthesis route satisfies a design goal comprises determining a yield value of the final product molecule.

37. The apparatus of claim 30, wherein the method further comprises:

performing a selected operation on at least one selected individual to produce a new individual; and

adding the individual produced by the selected operation to the population.

38. The apparatus of claim 30, wherein the selected operation is probabilistically chosen from the group of operations consisting of crossover, mutation, molecule noise and copy.