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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 2020, 63, 20, 11964-11971
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    A Turing Test for Molecular Generators
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    • Jacob T. Bush
      Jacob T. Bush
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
      More by Jacob T. Bush
      Orcidhttp://orcid.org/0000-0001-7165-0092
    • Peter Pogany
      Peter Pogany
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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      Orcidhttp://orcid.org/0000-0003-3536-0746
    • Stephen D. Pickett
      Stephen D. Pickett
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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      Orcidhttp://orcid.org/0000-0002-0958-9830
    • Mike Barker
      Mike Barker
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Andrew Baxter
      Andrew Baxter
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Sebastien Campos
      Sebastien Campos
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Anthony W. J. Cooper
      Anthony W. J. Cooper
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • David Hirst
      David Hirst
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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      Orcidhttp://orcid.org/0000-0001-9969-2104
    • Graham Inglis
      Graham Inglis
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Alan Nadin
      Alan Nadin
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Vipulkumar K. Patel
      Vipulkumar K. Patel
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Darren Poole
      Darren Poole
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • John Pritchard
      John Pritchard
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Yoshiaki Washio
      Yoshiaki Washio
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Gemma White
      Gemma White
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
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    • Darren V. S. Green*
      Darren V. S. Green
      GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
      *Email: [email protected]
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    Other Access OptionsSupporting Information (3)

    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2020, 63, 20, 11964–11971
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    https://doi.org/10.1021/acs.jmedchem.0c01148
    Published September 21, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    Machine learning approaches promise to accelerate and improve success rates in medicinal chemistry programs by more effectively leveraging available data to guide a molecular design. A key step of an automated computational design algorithm is molecule generation, where the machine is required to design high-quality, drug-like molecules within the appropriate chemical space. Many algorithms have been proposed for molecular generation; however, a challenge is how to assess the validity of the resulting molecules. Here, we report three Turing-inspired tests designed to evaluate the performance of molecular generators. Profound differences were observed between the performance of molecule generators in these tests, highlighting the importance of selection of the appropriate design algorithms for specific circumstances. One molecule generator, based on match molecular pairs, performed excellently against all tests and thus provides a valuable component for machine-driven medicinal chemistry design workflows.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c01148.

    • Experimental Details, Supplementary Figures (Figure S1-S4) and Supplementary Tables (Table S1-S4) (PDF)

    • Results of the Turing Test (CSV)

    • Full list of chemistry ideas (CSV)

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    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

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    This article is cited by 27 publications.

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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2020, 63, 20, 11964–11971
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.0c01148
    Published September 21, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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