OpenLB
Open Library of Bioscience
Advanced Search
ACS medicinal chemistry letters
Sep 12, 2024;15 (9): 1449-1455.

Allostery Illuminated: Harnessing AI and Machine Learning for Drug Discovery.

Maria-Jesus Blanco, Melissa J Buskes, Rajiv G Govindaraj, Jonathan J Ipsaro, Joann E Prescott-Roy, Anil K Padyana
Author Information
  1. Maria-Jesus Blanco: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States. ORCID
  2. Melissa J Buskes: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States. ORCID
  3. Rajiv G Govindaraj: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States.
  4. Jonathan J Ipsaro: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States.
  5. Joann E Prescott-Roy: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States.
  6. Anil K Padyana: Atavistik Bio, 101 Cambridgepark Drive, Cambridge, Massachusetts 02140, United States.
PMID: 39291033 DOI: 10.1021/acsmedchemlett.4c00260

Abstract

In the past several years there has been rapid adoption of artificial intelligence (AI) and machine learning (ML) tools for drug discovery. In this Microperspective, we comment on recent AI/ML applications to the discovery of allosteric modulators, focusing on breakthroughs with AlphaFold, structure-based drug discovery (SBDD), and medicinal chemistry applications. We discuss how these technologies are facilitating drug discovery and the remaining challenges to identify allosteric binding sites and ligands.

References

  1. Structure. 2023 Nov 2;31(11):1360-1374 [PMID: 37848030]
  2. Nat Chem. 2019 Dec;11(12):1113-1123 [PMID: 31659311]
  3. Biochem Pharmacol. 2024 Oct;228:116402 [PMID: 38945274]
  4. Science. 2024 Jun 21;384(6702):eadn6354 [PMID: 38753765]
  5. Curr Opin Struct Biol. 2024 Feb;84:102768 [PMID: 38215528]
  6. Sci Rep. 2017 Mar 03;7:42717 [PMID: 28256516]
  7. ACS Med Chem Lett. 2023 Jul 24;14(8):1095-1099 [PMID: 37583827]
  8. J Med Chem. 2020 Aug 27;63(16):8667-8682 [PMID: 32243158]
  9. ACS Med Chem Lett. 2023 Jun 30;14(7):901-915 [PMID: 37465301]
  10. Sci Rep. 2024 Apr 2;14(1):7526 [PMID: 38565852]
  11. J Phys Chem Lett. 2021 Apr 22;12(15):3724-3732 [PMID: 33843228]
  12. Curr Opin Struct Biol. 2023 Dec;83:102702 [PMID: 37716095]
  13. Life (Basel). 2022 Aug 19;12(8): [PMID: 36013446]
  14. Molecules. 2020 Jul 31;25(15): [PMID: 32751973]
  15. ACS Med Chem Lett. 2022 Oct 27;13(11):1691-1698 [PMID: 36385931]
  16. J Phys Chem B. 2022 Sep 1;126(34):6372-6383 [PMID: 35976160]
  17. Int J Mol Sci. 2023 Jul 15;24(14): [PMID: 37511247]
  18. Curr Opin Struct Biol. 2024 Apr;85:102774 [PMID: 38354652]
  19. Curr Opin Chem Biol. 2020 Jun;56:1-9 [PMID: 31622927]
  20. Curr Opin Struct Biol. 2024 Feb;84:102758 [PMID: 38171188]
  21. Nat Biotechnol. 2020 Feb;38(2):143-145 [PMID: 32001834]
  22. J Med Chem. 2018 Sep 27;61(18):8120-8135 [PMID: 30137981]
  23. J Chem Theory Comput. 2023 Jul 25;19(14):4355-4363 [PMID: 36948209]
  24. Science. 2021 Aug 20;373(6557):871-876 [PMID: 34282049]
  25. Bioinformatics. 2018 Aug 1;34(15):2590-2597 [PMID: 29547986]
  26. PLoS Comput Biol. 2017 Nov 10;13(11):e1005813 [PMID: 29125840]
  27. Nat Commun. 2023 Mar 1;14(1):1177 [PMID: 36859488]
  28. J Chem Inf Model. 2020 Oct 26;60(10):4664-4672 [PMID: 32931270]
  29. Nature. 2021 Aug;596(7873):583-589 [PMID: 34265844]
  30. J Med Chem. 2009 Nov 12;52(21):6752-6 [PMID: 19827778]
  31. Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444 [PMID: 34791371]
  32. Nat Methods. 2024 Aug;21(8):1514-1524 [PMID: 38744917]
  33. ACS Med Chem Lett. 2020 Mar 10;11(10):1810-1819 [PMID: 33062158]
  34. J Chem Inf Model. 2023 Sep 11;63(17):5484-5495 [PMID: 37635298]
  35. J Med Chem. 2020 Aug 27;63(16):8695-8704 [PMID: 32459965]
  36. Int J Mol Sci. 2022 Apr 21;23(9): [PMID: 35562983]
  37. J Phys Chem B. 2024 May 30;128(21):5157-5174 [PMID: 38647430]
  38. Drug Metab Dispos. 2021 Sep;49(9):822-832 [PMID: 34183376]
  39. Comput Struct Biotechnol J. 2024 Mar 24;23:1320-1338 [PMID: 38585646]
  40. Acta Crystallogr D Struct Biol. 2022 Jan 1;78(Pt 1):1-13 [PMID: 34981757]
  41. J Mol Biol. 2023 Jul 15;435(14):167994 [PMID: 36738985]
  42. J Mol Biol. 2022 Sep 15;434(17):167569 [PMID: 35378118]
  43. J Med Chem. 2016 May 26;59(10):4753-68 [PMID: 27067148]
  44. Mol Syst Biol. 2024 Mar;20(3):162-169 [PMID: 38291232]
  45. Nat Commun. 2024 Mar 21;15(1):2533 [PMID: 38514618]
  46. Cancer Discov. 2017 May;7(5):478-493 [PMID: 28193778]
  47. J Cheminform. 2020 Nov 17;12(1):70 [PMID: 33292482]
  48. J Med Chem. 2024 Apr 25;67(8):6508-6518 [PMID: 38568752]
  49. Science. 2023 Mar 10;379(6636):996-1003 [PMID: 36893255]
  50. Cells. 2022 Mar 07;11(5): [PMID: 35269537]
  51. ACS Med Chem Lett. 2023 Mar 08;14(4):376-385 [PMID: 37077380]
  52. J Cheminform. 2021 Sep 25;13(1):72 [PMID: 34563256]
  53. Science. 2019 Aug 9;365(6453): [PMID: 31395756]
Journal Article Review
Article has an altmetric score of 6

Word Cloud

Created with Highcharts 10.0.0discoverydrugAIapplicationsallostericpastseveralyearsrapidadoptionartificialintelligencemachinelearningMLtoolsMicroperspectivecommentrecentAI/MLmodulatorsfocusingbreakthroughsAlphaFoldstructure-basedSBDDmedicinalchemistrydiscusstechnologiesfacilitatingremainingchallengesidentifybindingsitesligandsAllosteryIlluminated:HarnessingMachineLearningDrugDiscovery

Similar Articles

Cited By