journal article·2024-12-10

Exploring Molecules with Low Viscosity: Using Physics-Based Simulations and De Novo Design by Applying Reinforcement Learning

Nobuyuki N. Matsuzawa, Hiroyuki Maeshima, Keisuke Hayashi, Tatsuhito Ando, Mohammad Atif Faiz Afzal, Kyle Marshall, Benjamin J. Coscia, Andrea R. Browning, Alexander Goldberg, Mathew D. Halls, Karl Leswing, Mayank Misra, Farhad Ramezanghorbani, Tsuguo Morisato

Chemistry of Materials· Volume 36· Issue 23
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Abstract

Molecules with viscosities lower than those of conventional organic solvents are highly sought after for applications in electrochemical devices such as batteries and capacitors. These molecules improve the electrical resistance of devices, enhancing their efficiency, especially at low temperatures. To identify new molecules with low viscosities, we conducted extensive molecular dynamics (MD) simulations on 10,000 molecules selected from the GDB-17 chemical structure database, specifically choosing molecules with fewer than 12 heavy atoms. Additionally, we performed density functional theory (DFT) calculations to determine the energies of the highest occupied molecular orbitals (HOMO) of these molecules as a surrogate for the oxidation potential. We used the data on viscosity and HOMO levels as training sets to develop machine-learning models that predict these properties. Using these models, we carried out molecular de novo design using the REINVENT method, a reinforcement-learning approach utilizing SMILES strings. This method aimed to identify molecules that minimize viscosity while maintaining sufficiently low HOMO levels for stability. The approach successfully identified new chemical structures with viscosities below 2 mPa·s and suitably low HOMO energies. We synthesized a novel compound from the top candidates and validated our predictions experimentally. The experimental results closely matched our predictions, demonstrating that combining physics-based simulations with reinforcement learning is an effective strategy for designing novel molecules with targeted properties.
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Research context

OpenAlex topics: Computational Drug Discovery Methods · Machine Learning in Materials Science · Process Optimization and Integration

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Engineering Division, Panasonic Industry Co., Ltd., 1006 Kadoma, Kadoma City, Osaka 571-8506, Japan

Schrödinger Inc., 101 SW Main Street, Suite 1300, Portland, Oregon 97204, United States

Schrödinger Inc., 9868 Scranton Road, Suite 3200, San Diego, California 92121, United States

Schrödinger Inc., 120 West 45th Street, 17th Floor, New York, New York 10036, United States

Schrödinger K.K., 13F Marunouchi Trust Tower North,1-8-1 Marunouchi Chiyoda-ku, Tokyo 100-0005, Japan

References (66)

Show source-provided references
1. 10.1016/j.esci.2023.10017010.1016/j.esci.2023.100170 ↗
2. 10.3390/ma1522816610.3390/ma15228166 ↗
3. 10.1021/acs.chemrev.2c0037410.1021/acs.chemrev.2c00374 ↗
4. 10.1149/1.145340710.1149/1.1453407 ↗
5. 10.1039/C9NA00374F10.1039/C9NA00374F ↗
6. 10.1149/1.183749510.1149/1.1837495 ↗
7. Viswanath D. S. · 2007
8. 10.1002/kin.55019010710.1002/kin.550190107 ↗
9. 10.1073/pnas.202035711810.1073/pnas.2020357118 ↗
10. 10.1149/05827.0071ecst10.1149/05827.0071ecst ↗
11. 10.1016/S0378-7753(00)00578-410.1016/S0378-7753(00)00578-4 ↗
12. 10.1016/S0378-7753(03)00154-X10.1016/S0378-7753(03)00154-X ↗
13. 10.1038/npjcompumats.2015.1010.1038/npjcompumats.2015.10 ↗
14. 10.1063/1.481232310.1063/1.4812323 ↗
15. 10.1039/D3DD00153A10.1039/D3DD00153A ↗
16. 10.1021/acs.jpcc.8b0291310.1021/acs.jpcc.8b02913 ↗
17. 10.1021/acs.jpclett.6b0165710.1021/acs.jpclett.6b01657 ↗
18. 10.1021/acs.jpca.9b1099810.1021/acs.jpca.9b10998 ↗
19. 10.1038/sdata.2016.13410.1038/sdata.2016.134 ↗
20. 10.1038/s41524-022-00906-410.1038/s41524-022-00906-4 ↗
21. 10.1063/5.004430610.1063/5.0044306 ↗
22. 10.1021/acscentsci.7b0057210.1021/acscentsci.7b00572 ↗
23. Jin, W.; Barzilay, R.; Jaakkola, T. In Junction Tree Variational Autoencoder for Molecular Graph Generation, International Conference on Machine Learning; PMLR, 2018; pp 2323–2332.
24. 10.1186/s13321-017-0235-x10.1186/s13321-017-0235-x ↗
25. 10.1038/s41598-019-47148-x10.1038/s41598-019-47148-x ↗
26. 10.1038/s41587-019-0224-x10.1038/s41587-019-0224-x ↗
27. 10.1080/14686996.2017.140142410.1080/14686996.2017.1401424 ↗
28. 10.1186/s13321-019-0397-910.1186/s13321-019-0397-9 ↗
29. Yang L. · ACM Comput. Surv. · 2023 · 56 · 105
30. 10.1038/s42256-022-00580-710.1038/s42256-022-00580-7 ↗
31. 10.1039/C8SC05372C10.1039/C8SC05372C ↗
32. 10.1021/acs.jpca.1c0458710.1021/acs.jpca.1c04587 ↗
33. 10.1021/acs.jpca.2c0422110.1021/acs.jpca.2c04221 ↗
34. 10.1021/acs.jmedchem.3c0205110.1021/acs.jmedchem.3c02051 ↗
35. 10.1021/acs.jcim.0c0132810.1021/acs.jcim.0c01328 ↗
36. Bowers, K. J.; Chow, E.; Xu, H.; Dror, R. O.; Eastwood, M. P.; Gregersen, B. A.; Klepeis, J. L.; Kolossvary, I.; Moraes, M. A.; Sacerdoti, F. D.; Salmon, J. K.; Shan, Y.; Shaw, D. E. In Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters, Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, SC’06, 2006; pp 84–96.10.1145/1188455.1188544 ↗
37. Schrödinger Release 2019-4: Desmond Molecular Dynamics System; Schrödinger: New York, NY, 2019. https://www.schrodinger.com/products/desmond.
38. Schrodinger Release 2019-4: Materials Science Suite; Schrödinger, LLC: New York, 2019. https://www.schrodinger.com/platform/materials-science.
39. 10.1021/ja962176010.1021/ja9621760 ↗
40. 10.1021/acs.jctc.5b0086410.1021/acs.jctc.5b00864 ↗
41. 10.1039/tf959550002810.1039/tf9595500028 ↗
42. 10.33011/livecoms.1.1.632410.33011/livecoms.1.1.6324 ↗
43. 10.1063/1.47400210.1063/1.474002 ↗
44. 10.1088/1742-6596/1556/1/01204810.1088/1742-6596/1556/1/012048 ↗
45. 10.1063/1.46491310.1063/1.464913 ↗
46. 10.1103/PhysRevB.37.78510.1103/PhysRevB.37.785 ↗
47. 10.1063/1.167490210.1063/1.1674902 ↗
48. 10.1063/1.44879910.1063/1.448799 ↗
49. 10.1063/1.44880010.1063/1.448800 ↗
50. 10.1063/1.44897510.1063/1.448975 ↗
51. 10.1002/qua.2448110.1002/qua.24481 ↗
52. Jaguar Release 2019-4: Materials Science Suite; Schrödinger, LLC: New York, 2019. https://www.schrodinger.com/platform/jaguar.
53. 10.4155/fmc-2016-009310.4155/fmc-2016-0093 ↗
54. 10.2307/237121910.2307/2371219 ↗
55. Landrum, G. RDKit: Open-Source Cheminformatics, 2020. http://www.rdkit.org.
56. 10.3233/IDA-13059210.3233/IDA-130592 ↗
57. REINVENT Code, 2020. https://github.com/MarcusOlivecrona/REINVENT.
58. 10.1073/pnas.48.6.90510.1073/pnas.48.6.905 ↗
59. 10.1021/ci300415d10.1021/ci300415d ↗
60. 10.1021/ci100050t10.1021/ci100050t ↗
61. 10.1126/science.132.3434.111510.1126/science.132.3434.1115 ↗
62. 10.1186/s13321-024-00820-510.1186/s13321-024-00820-5 ↗
63. 10.1021/je970225y10.1021/je970225y ↗
64. 10.1021/je020116610.1021/je0201166 ↗
65. 10.1021/ie50448a02210.1021/ie50448a022 ↗
66. 10.1080/0098644870896048710.1080/00986448708960487 ↗