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A paradigm shift in structural biology

Nature Methods volume 19, pages 20–23 (2022)Cite this article

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The release of protein structure predictions from AlphaFold will increase the number of protein structural models by almost three orders of magnitude. Structural biology and bioinformatics will never be the same, and the need for incisive experimental approaches will be greater than ever. Combining these advances in structure prediction with recent advances in cryo-electron microscopy suggests a new paradigm for structural biology.

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Fig. 1: Three-dimensional structure predicted by AlphaFold for human BRD4.
Fig. 2: A protein interaction network for BRD4 generated by the String database14.
Fig. 3: The number of entries at resolutions better than 6 Å released by the Electron Microscopy Data Bank per year from 2012 to 2021.

References

  1. Kryshtafovych, A., Schwede, T., Topf, M., Fidelis, K. & Moult, J. Proteins 89, 1607–1617 (2021).

    Article  CAS  Google Scholar 

  2. Jumper, J. et al. Nature 596, 583–589 (2021).

    Article  CAS  Google Scholar 

  3. Baek, M. et al. Science 373, 871–876 (2021).

    Article  CAS  Google Scholar 

  4. Tunyasuvunakool, K. et al. Nature 596, 590–596 (2021).

    Article  CAS  Google Scholar 

  5. Varadi, M. et al. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab1061 (2021).

  6. wwPDB consortium. Nucleic Acids Res. 47, D520–D528 (2019).

    Article  Google Scholar 

  7. Kuhn, T. S. The Structure of Scientific Revolutions (Univ. of Chicago Press, 1962).

  8. Akdel, M. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.09.26.461876 (2021).

  9. Ruff, K. M. & Pappu, R. V. J. Mol. Biol. 433, 167208 (2021).

    Article  CAS  Google Scholar 

  10. Burke, D. F. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.11.08.467664 (2021).

  11. Vamathevan, J. et al. Nat. Rev. Drug Discov. 18, 463–477 (2019).

    Article  CAS  Google Scholar 

  12. Evans, R. et al. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 (2021).

  13. Humphreys, I. R. et al. Science https://doi.org/10.1126/science.abm4805 (2021).

  14. Szklarczyk, D. et al. Nucleic Acids Res. 49(D1), D605–D612 (2021).

    Article  CAS  Google Scholar 

  15. Walls, A. C. et al. Cell 181, 281–292.e286 (2020).

    Article  CAS  Google Scholar 

  16. Wrapp, D. et al. Science 367, 1260–1263 (2020).

    Article  CAS  Google Scholar 

  17. Mahamid, J. et al. Science 351, 969–972 (2016).

    Article  CAS  Google Scholar 

  18. Marx, V. Nat. Methods 15, 575–578 (2018).

    Article  CAS  Google Scholar 

  19. Wagner, F. R. et al. Nat. Protoc. 15, 2041–2070 (2020).

    Article  CAS  Google Scholar 

  20. Schaffer, M. et al. Nat. Methods 16, 757–762 (2019).

    Article  CAS  Google Scholar 

  21. Narayan, K. & Subramaniam, S. Nat. Methods 12, 1021–1031 (2015).

    Article  CAS  Google Scholar 

  22. Swedlow, J. R. & Collinson, L. Nature 599, 39–40 (2021).

    Article  CAS  Google Scholar 

  23. O’Reilly, F. J. et al. Science 369, 554–557 (2020).

    Article  Google Scholar 

Download references

Acknowledgements

S.S. is supported by awards from a Canada Excellence Research Chair Award, the VGH Foundation, Genome BC and the Tai Hung Fai Charitable Foundation. G.J.K. is supported by EMBL-EBI, with funding from the EMBL member states, as well as by the Wellcome Trust. We thank Z. Wang (EMBL-EBI) for producing Fig. 3 and D. Singer and A. Singh (National Cancer Institute, US National Institutes of Health) for comments.

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Authors and Affiliations

  1. University of British Columbia, Vancouver, BC, Canada

    Sriram Subramaniam

  2. Gandeeva Therapeutics Inc, Vancouver, BC, Canada

    Sriram Subramaniam

  3. European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK

    Gerard J. Kleywegt

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  1. Sriram Subramaniam
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  2. Gerard J. Kleywegt
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Correspondence to Sriram Subramaniam or Gerard J. Kleywegt.

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Competing interests

S.S. is founder and CEO of Gandeeva Therapeutics Inc., a drug discovery company based in Vancouver, BC, Canada.

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Subramaniam, S., Kleywegt, G.J. A paradigm shift in structural biology. Nat Methods 19, 20–23 (2022). https://doi.org/10.1038/s41592-021-01361-7

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