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Big data and benchmarking initiatives to bridge the gap from AlphaFold to drug design

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AlphaFold is a breakthrough in protein structure prediction, but limitations in its application to computation- and structure-guided drug discovery remain. As with structure prediction, public-domain data and benchmarking initiatives will be essential to advance the field of computational drug design.

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Fig. 1: Comparison of inactive and active conformations of Cbl-b, the latter induced by phosphorylation.
Fig. 2: Comparison of ligand-free and ligand-bound pockets.

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Acknowledgements

The Structural Genomics Consortium is a registered charity (UK charities commission no. 1097737) that receives funds from Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Genome Canada through the Ontario Genomics Institute (OGI-196), EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant 875510), Janssen, Merck (known as EMD in Canada and the United States), Pfizer and Takeda.

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Authors and Affiliations

  1. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada

    Matthieu Schapira, Levon Halabelian, Cheryl H. Arrowsmith & Rachel J. Harding

  2. Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada

    Matthieu Schapira, Levon Halabelian & Rachel J. Harding

  3. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Cheryl H. Arrowsmith

  4. Princess Margaret Cancer Centre, Toronto, Ontario, Canada

    Cheryl H. Arrowsmith

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  1. Matthieu Schapira
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  2. Levon Halabelian
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  3. Cheryl H. Arrowsmith
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  4. Rachel J. Harding
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Contributions

M.S. and R.J.H. created the figures. M.S., R.J.H., L.H. and C.H.A. conceived and wrote this Commentary.

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Correspondence to Rachel J. Harding.

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The authors declare no competing interests.

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Schapira, M., Halabelian, L., Arrowsmith, C.H. et al. Big data and benchmarking initiatives to bridge the gap from AlphaFold to drug design. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01570-z

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