84
views
0
recommends
+1 Recommend
1 collections
    1
    shares
       
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Engines of discovery: Computers in advanced synthesis planning and identification of drug candidates

      AsiaChem Magazine
      Israel Chemical Society (ICS)
      Drug discovery
      Bookmark

            Abstract

            After over five decades of efforts, computers have recently begun to plan chemical syntheses of complex targets at a level comparable to human experts. With this milestone achieved, it is now time to ponder not only how the machines will accelerate and multiplex synthetic design, but also how they will guide the discovery of new targets having desired properties.

            Content

            Author and article information

            Journal
            AsiaChem Magazine
            ACM
            Israel Chemical Society (ICS)
            25 November 2020
            25 November 2020
            : 1
            : 1
            : 42-49
            Article
            10.51167/acm00010
            2b4da520-9f8a-43cc-b028-17788c470552

            Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.


            Chemistry
            Drug discovery

            References

            1. Vléduts G.É., Finn V.K.. Creating a machine language for organic chemistry. Information Storage and Retrieval. Vol. 1(2-3):101–116. 1963. Elsevier BV. [Cross Ref]

            2. Corey E. J., Wipke W. Todd. Computer-Assisted Design of Complex Organic Syntheses. Science. Vol. 166(3902):178–192. 1969. American Association for the Advancement of Science (AAAS). [Cross Ref]

            3. van Rozendaal Erik L. M., Ott Martin A., Scheeren Hans W.. A LHASA analysis of taxol. Recueil des Travaux Chimiques des Pays-Bas. Vol. 113(5):297–303. 1994. Wiley. [Cross Ref]

            4. Tanaka Akio, Kawai Takashi, Takabatake Tetsuhiko, Oka Noriko, Okamoto Hideho, Bersohn Malcolm. Synthesis of an azaspirane via Birch reduction alkylation prompted by suggestions from a computer program. Tetrahedron Letters. Vol. 47(38):6733–6737. 2006. Elsevier BV. [Cross Ref]

            5. Silver David, Huang Aja, Maddison Chris J., Guez Arthur, Sifre Laurent, van den Driessche George, Schrittwieser Julian, Antonoglou Ioannis, Panneershelvam Veda, Lanctot Marc, Dieleman Sander, Grewe Dominik, Nham John, Kalchbrenner Nal, Sutskever Ilya, Lillicrap Timothy, Leach Madeleine, Kavukcuoglu Koray, Graepel Thore, Hassabis Demis. Mastering the game of Go with deep neural networks and tree search. Nature. Vol. 529(7587):484–489. 2016. Springer Science and Business Media LLC. [Cross Ref]

            6. Senior Andrew W., Evans Richard, Jumper John, Kirkpatrick James, Sifre Laurent, Green Tim, Qin Chongli, Žídek Augustin, Nelson Alexander W. R., Bridgland Alex, Penedones Hugo, Petersen Stig, Simonyan Karen, Crossan Steve, Kohli Pushmeet, Jones David T., Silver David, Kavukcuoglu Koray, Hassabis Demis. Improved protein structure prediction using potentials from deep learning. Nature. Vol. 577(7792):706–710. 2020. Springer Science and Business Media LLC. [Cross Ref]

            7. Segler Marwin H. S., Preuss Mike, Waller Mark P.. Planning chemical syntheses with deep neural networks and symbolic AI. Nature. Vol. 555(7698):604–610. 2018. Springer Science and Business Media LLC. [Cross Ref]

            8. Coley Connor W., Thomas Dale A., Lummiss Justin A. M., Jaworski Jonathan N., Breen Christopher P., Schultz Victor, Hart Travis, Fishman Joshua S., Rogers Luke, Gao Hanyu, Hicklin Robert W., Plehiers Pieter P., Byington Joshua, Piotti John S., Green William H., Hart A. John, Jamison Timothy F., Jensen Klavs F.. A robotic platform for flow synthesis of organic compounds informed by AI planning. Science. Vol. 365(6453)2019. American Association for the Advancement of Science (AAAS). [Cross Ref]

            9. Schwaller Philippe, Petraglia Riccardo, Zullo Valerio, Nair Vishnu H., Haeuselmann Rico Andreas, Pisoni Riccardo, Bekas Costas, Iuliano Anna, Laino Teodoro. Predicting retrosynthetic pathways using transformer-based models and a hyper-graph exploration strategy. Chemical Science. Vol. 11(12):3316–3325. 2020. Royal Society of Chemistry (RSC). [Cross Ref]

            10. Mikulak-Klucznik Barbara, Gołębiowska Patrycja, Bayly Alison A., Popik Oskar, Klucznik Tomasz, Szymkuć Sara, Gajewska Ewa P., Dittwald Piotr, Staszewska-Krajewska Olga, Beker Wiktor, Badowski Tomasz, Scheidt Karl A., Molga Karol, Mlynarski Jacek, Mrksich Milan, Grzybowski Bartosz A.. Computational planning of the synthesis of complex natural products. Nature. Vol. 588(7836):83–88. 2020. Springer Science and Business Media LLC. [Cross Ref]

            11. Fialkowski Marcin, Bishop Kyle J. M., Chubukov Victor A., Campbell Christopher J., Grzybowski Bartosz A.. Architecture and Evolution of Organic Chemistry. Angewandte Chemie International Edition. Vol. 44(44):7263–7269. 2005. Wiley. [Cross Ref]

            12. Grzybowski Bartosz A., Bishop Kyle J. M., Kowalczyk Bartlomiej, Wilmer Christopher E.. The 'wired' universe of organic chemistry. Nature Chemistry. Vol. 1(1):31–36. 2009. Springer Science and Business Media LLC. [Cross Ref]

            13. Gothard Chris M., Soh Siowling, Gothard Nosheen A., Kowalczyk Bartlomiej, Wei Yanhu, Baytekin Bilge, Grzybowski Bartosz A.. Rewiring Chemistry: Algorithmic Discovery and Experimental Validation of One-Pot Reactions in the Network of Organic Chemistry. Angewandte Chemie International Edition. Vol. 51(32):7922–7927. 2012. Wiley. [Cross Ref]

            14. Szymkuć Sara, Gajewska Ewa P., Klucznik Tomasz, Molga Karol, Dittwald Piotr, Startek Michał, Bajczyk Michał, Grzybowski Bartosz A.. Computer‐Assisted Synthetic Planning: The End of the Beginning. Angewandte Chemie International Edition. Vol. 55(20):5904–5937. 2016. Wiley. [Cross Ref]

            15. Klucznik Tomasz, Mikulak-Klucznik Barbara, McCormack Michael P., Lima Heather, Szymkuć Sara, Bhowmick Manishabrata, Molga Karol, Zhou Yubai, Rickershauser Lindsey, Gajewska Ewa P., Toutchkine Alexei, Dittwald Piotr, Startek Michał P., Kirkovits Gregory J., Roszak Rafał, Adamski Ariel, Sieredzińska Bianka, Mrksich Milan, Trice Sarah L.J., Grzybowski Bartosz A.. Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory. Chem. Vol. 4(3):522–532. 2018. Elsevier BV. [Cross Ref]

            16. Molga Karol, Gajewska Ewa P., Szymkuć Sara, Grzybowski Bartosz A.. The logic of translating chemical knowledge into machine-processable forms: a modern playground for physical-organic chemistry. Reaction Chemistry & Engineering. Vol. 4(9):1506–1521. 2019. Royal Society of Chemistry (RSC). [Cross Ref]

            17. Gajewska Ewa P., Szymkuć Sara, Dittwald Piotr, Startek Michał, Popik Oskar, Mlynarski Jacek, Grzybowski Bartosz A.. Algorithmic Discovery of Tactical Combinations for Advanced Organic Syntheses. Chem. Vol. 6(1):280–293. 2020. Elsevier BV. [Cross Ref]

            18. Badowski Tomasz, Gajewska Ewa P., Molga Karol, Grzybowski Bartosz A.. Synergy Between Expert and Machine‐Learning Approaches Allows for Improved Retrosynthetic Planning. Angewandte Chemie International Edition. Vol. 59(2):725–730. 2020. Wiley. [Cross Ref]

            19. Corey E. J.. General methods for the construction of complex molecules. Pure and Applied Chemistry. Vol. 14(1):19–38. 1967. Walter de Gruyter GmbH. [Cross Ref]

            20. Corey E. J., Long Alan K., Rubenstein Stewart D.. Computer-Assisted Analysis in Organic Synthesis. Science. Vol. 228(4698):408–418. 1985. American Association for the Advancement of Science (AAAS). [Cross Ref]

            21. Cook Anthony, Johnson A. Peter, Law James, Mirzazadeh Mahdi, Ravitz Orr, Simon Aniko. Computer‐aided synthesis design: 40 years on. WIREs Computational Molecular Science. Vol. 2(1):79–107. 2012. Wiley. [Cross Ref]

            22. Beker Wiktor, Gajewska Ewa P., Badowski Tomasz, Grzybowski Bartosz A.. Prediction of Major Regio‐, Site‐, and Diastereoisomers in Diels–Alder Reactions by Using Machine‐Learning: The Importance of Physically Meaningful Descriptors. Angewandte Chemie International Edition. Vol. 58(14):4515–4519. 2019. Wiley. [Cross Ref]

            23. Kowalik Mikołaj, Gothard Chris M., Drews Aaron M., Gothard Nosheen A., Weckiewicz Alex, Fuller Patrick E., Grzybowski Bartosz A., Bishop Kyle J. M.. Parallel Optimization of Synthetic Pathways within the Network of Organic Chemistry. Angewandte Chemie International Edition. Vol. 51(32):7928–7932. 2012. Wiley. [Cross Ref]

            24. Patel Ramesh N.. Biocatalysis for synthesis of pharmaceuticals. Bioorganic & Medicinal Chemistry. Vol. 26(7):1252–1274. 2018. Elsevier BV. [Cross Ref]

            25. Molga Karol, Dittwald Piotr, Grzybowski Bartosz A.. Navigating around Patented Routes by Preserving Specific Motifs along Computer-Planned Retrosynthetic Pathways. Chem. Vol. 5(2):460–473. 2019. Elsevier BV. [Cross Ref]

            26. Szymkuć Sara, Gajewska Ewa P., Molga Karol, Wołos Agnieszka, Roszak Rafał, Beker Wiktor, Moskal Martyna, Dittwald Piotr, Grzybowski Bartosz A.. Computer-generated “synthetic contingency” plans at times of logistics and supply problems: scenarios for hydroxychloroquine and remdesivir. Chemical Science. Vol. 11(26):6736–6744. 2020. Royal Society of Chemistry (RSC). [Cross Ref]

            27. Lin Yingfu, Zhang Zirong, Mahjour Babak, Wang Di, Zhang Rui, Shim Eunjae, McGrath Andrew, Shen Yuning, Brugger Nadia, Turnbull Rachel, Jasty Shashi, Trice Sarah, Cernak Tim. Reinforcing the Supply Chain of COVID-19 Therapeutics with Expert-Coded Retrosynthetic Software. American Chemical Society (ACS). [Cross Ref]

            28. Molga Karol, Dittwald Piotr, Grzybowski Bartosz A.. Computational design of syntheses leading to compound libraries or isotopically labelled targets. Chemical Science. Vol. 10(40):9219–9232. 2019. Royal Society of Chemistry (RSC). [Cross Ref]

            29. Wołos Agnieszka, Roszak Rafał, Żądło-Dobrowolska Anna, Beker Wiktor, Mikulak-Klucznik Barbara, Spólnik Grzegorz, Dygas Mirosław, Szymkuć Sara, Grzybowski Bartosz A.. Synthetic connectivity, emergence, and self-regeneration in the network of prebiotic chemistry. Science. Vol. 369(6511)2020. American Association for the Advancement of Science (AAAS). [Cross Ref]

            30. Beker Wiktor, Wołos Agnieszka, Szymkuć Sara, Grzybowski Bartosz A.. Minimal-uncertainty prediction of general drug-likeness based on Bayesian neural networks. Nature Machine Intelligence. Vol. 2(8):457–465. 2020. Springer Science and Business Media LLC. [Cross Ref]

            31. Gao Wenhao, Coley Connor W.. The Synthesizability of Molecules Proposed by Generative Models. Journal of Chemical Information and Modeling. Vol. 60(12):5714–5723. 2020. American Chemical Society (ACS). [Cross Ref]

            32. Steiner Sebastian, Wolf Jakob, Glatzel Stefan, Andreou Anna, Granda Jarosław M., Keenan Graham, Hinkley Trevor, Aragon-Camarasa Gerardo, Kitson Philip J., Angelone Davide, Cronin Leroy. Organic synthesis in a modular robotic system driven by a chemical programming language. Science. Vol. 363(6423)2019. American Association for the Advancement of Science (AAAS). [Cross Ref]

            33. Badowski Tomasz, Molga Karol, Grzybowski Bartosz A.. Selection of cost-effective yet chemically diverse pathways from the networks of computer-generated retrosynthetic plans. Chemical Science. Vol. 10(17):4640–4651. 2019. Royal Society of Chemistry (RSC). [Cross Ref]

            Comments

            Comment on this article