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Structural biology is solved — now what?

Nature Methods volume 19, pages 24–26 (2022)Cite this article

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The splendid computational success of AlphaFold and RoseTTAFold in solving the 60-year-old problem of protein folding raises an obvious question: what new avenues should structural biology explore? We propose a strong pivot toward the goal of reading mechanism and function directly from the amino acid sequence. This ambitious goal will require new data analytical tools and an extensive database of the atomic-level structural trajectories traced out on energy landscapes as proteins perform their function.

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Fig. 1: Experimentally determined energy landscapes for the protein ryanodine receptor 1 (RYR1) with and without ligands.
Fig. 2: Series of energy landscapes for the hemagglutinin fusion peptide membrane insertion simulated by molecular dynamics.

References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Bernstein, F. C. et al. J. Mol. Biol. 112, 535–542 (1977).

    Article  CAS  Google Scholar 

  4. LeCun, Y., Bengio, Y. & Hinton, G. Nature 521, 436–444 (2015).

    Article  CAS  Google Scholar 

  5. Dashti, A. et al. Proc. Natl Acad. Sci. USA 111, 17492–17497 (2014).

    Article  CAS  Google Scholar 

  6. Hosseinizadeh, A. et al. Nat. Methods 14, 877–881 (2017).

    Article  CAS  Google Scholar 

  7. Dashti, A. et al. Nat. Commun. 11, 4734 (2020).

    Article  CAS  Google Scholar 

  8. Zhong, E. D., Bepler, T., Berger, B. & Davis, J. H. Nat. Methods 18, 176–185 (2021).

    Article  CAS  Google Scholar 

  9. Punjani, A. & Fleet, D. J. J. Struct. Biol. 213, 107702 (2021).

    Article  CAS  Google Scholar 

  10. Giraldo-Barreto, J. et al. Sci. Rep. 11, 13657 (2021).

    Article  CAS  Google Scholar 

  11. Frauenfelder, H., Sligar, S. G. & Wolynes, P. G. Science 254, 1598–1603 (1991).

    Article  CAS  Google Scholar 

  12. Ourmazd, A. Nat. Methods 16, 941–944 (2019).

    Article  CAS  Google Scholar 

  13. Schwander, P., Fung, R., Phillips, G. N. & Ourmazd, A. New J. Phys. 12, 035007 (2010).

    Article  Google Scholar 

  14. Schwander, P., Fung, R. & Ourmazd, A. Phil. Trans. R. Soc. Lond. B 369, 20130567 (2014).

    Article  CAS  Google Scholar 

  15. Nakane, T., Kimanius, D., Lindahl, E. & Scheres, S. H. eLife 7, e36861 (2018).

    Article  Google Scholar 

  16. Giraldo-Barreto, J. Sci. Rep. 11, 13657 (2021).

  17. Hosseinizadeh, A. et al. Nature 599, 697–701 (2021).

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge valuable discussions with past and present members of the University of Wisconsin Milwaukee data science group. The development of underlying techniques was supported by the US Department of Energy, Office of Science, Basic Energy Sciences, under award DE-SC0002164 (underlying dynamical techniques) and by the US National Science Foundation under awards STC-1231306 (underlying data analytical techniques) and DBI-2029533 (underlying analytical models).

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Authors and Affiliations

  1. University of Wisconsin Milwaukee, Milwaukee, WI, USA

    Abbas Ourmazd

  2. Department of Biochemistry & Molecular Biology and the Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA

    Keith Moffat

  3. Baltimore, MD, USA

    Eaton Edward Lattman

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  1. Abbas Ourmazd
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Correspondence to Abbas Ourmazd.

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Ourmazd, A., Moffat, K. & Lattman, E.E. Structural biology is solved — now what?. Nat Methods 19, 24–26 (2022). https://doi.org/10.1038/s41592-021-01357-3

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