Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data

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dc.citation.articleNumber13
dc.citation.journalTitleFrontiers in Molecular Biosciences
dc.citation.volumeNumber4
dc.contributor.authorDevaurs, Didier
dc.contributor.authorAntunes, Dinler A.
dc.contributor.authorPapanastasiou, Malvina
dc.contributor.authorMoll, Mark
dc.contributor.authorRicklin, Daniel
dc.contributor.authorLambris, John D.
dc.contributor.authorKavraki, Lydia E.
dc.date.accessioned2017-05-05T19:00:53Z
dc.date.available2017-05-05T19:00:53Z
dc.date.issued2017
dc.description.abstractMonitoring 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 aļ¾ singleļ¾ 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.
dc.identifier.citationDevaurs, Didier, Antunes, Dinler A., Papanastasiou, Malvina, et al.. "Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data." <i>Frontiers in Molecular Biosciences,</i> 4, (2017) Frontiers Media S.A.: https://doi.org/10.3389/fmolb.2017.00013.
dc.identifier.doihttps://doi.org/10.3389/fmolb.2017.00013
dc.identifier.urihttps://hdl.handle.net/1911/94188
dc.language.isoeng
dc.publisherFrontiers Media S.A.
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordprotein conformational sampling
dc.subject.keywordcoarse-grained conformational sampling
dc.subject.keywordmolecular dynamics
dc.subject.keywordexperimental data fitting
dc.subject.keywordhydrogen/deuterium exchange
dc.subject.keywordmass spectrometry
dc.subject.keywordnuclear magnetic resonance spectroscopy
dc.subject.keywordX-ray crystallography
dc.titleCoarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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