Coarse-grained conformational sampling of protein structure improves the fit to experimental hydrogen-exchange data

Devaurs, Didier and Antunes, Dinler A. and Papanastasiou, Malvina and Moll, Mark and Ricklin, Daniel and Lambris, John D. and Kavraki, Lydia E. (2017) Coarse-grained conformational sampling of protein structure improves the fit to experimental hydrogen-exchange data. Frontiers in Molecular Biosciences, 4. 13. ISSN 2296-889X (https://doi.org/10.3389/fmolb.2017.00013)

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Abstract

Monitoring hydrogen/deuterium exchange (HDX) undergone by a protein in solution produces experimental data that translates into valuable information about the protein's structure. Data produced by HDX experiments is often interpreted using a crystal structure of the protein, when available. However, it has been shown that the correspondence between experimental HDX data and crystal structures is often not satisfactory. This creates difficulties when trying to perform a structural analysis of the HDX data. In this paper, we evaluate several strategies to obtain a conformation providing a good fit to the experimental HDX data, which is a premise of an accurate structural analysis. We show that performing molecular dynamics simulations can be inadequate to obtain such conformations, and we propose a novel methodology involving a coarse-grained conformational sampling approach instead. By extensively exploring the intrinsic flexibility of a protein with this approach, we produce a conformational ensemble from which we extract a single conformation providing a good fit to the experimental HDX data. We successfully demonstrate the applicability of our method to four small and medium-sized proteins.

ORCID iDs

Devaurs, Didier ORCID logoORCID: https://orcid.org/0000-0002-3415-9816, Antunes, Dinler A., Papanastasiou, Malvina, Moll, Mark, Ricklin, Daniel, Lambris, John D. and Kavraki, Lydia E.;
  • Item type:Article
    ID code:90272
    Dates:
    Date
    Event
    10 March 2017
    Published
    24 February 2017
    Accepted
    Subjects:Science > Natural history > Biology
    Department:UNSPECIFIED
    Depositing user: Pure Administrator
    Date deposited:16 Aug 2024 09:44
    Last modified:01 Sep 2024 01:49
    URI:https://strathprints.strath.ac.uk/id/eprint/90272
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