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Structural biology is solved — now what?

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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.

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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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  2. Keith Moffat
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  3. Eaton Edward Lattman
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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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