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

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dc.citation.articleNumber13en_US
dc.citation.journalTitleFrontiers in Molecular Biosciencesen_US
dc.citation.volumeNumber4en_US
dc.contributor.authorDevaurs, Didieren_US
dc.contributor.authorAntunes, Dinler A.en_US
dc.contributor.authorPapanastasiou, Malvinaen_US
dc.contributor.authorMoll, Marken_US
dc.contributor.authorRicklin, Danielen_US
dc.contributor.authorLambris, John D.en_US
dc.contributor.authorKavraki, Lydia E.en_US
dc.date.accessioned2017-05-05T19:00:53Zen_US
dc.date.available2017-05-05T19:00:53Zen_US
dc.date.issued2017en_US
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.en_US
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.en_US
dc.identifier.doihttps://doi.org/10.3389/fmolb.2017.00013en_US
dc.identifier.urihttps://hdl.handle.net/1911/94188en_US
dc.language.isoengen_US
dc.publisherFrontiers Media S.A.en_US
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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordprotein conformational samplingen_US
dc.subject.keywordcoarse-grained conformational samplingen_US
dc.subject.keywordmolecular dynamicsen_US
dc.subject.keywordexperimental data fittingen_US
dc.subject.keywordhydrogen/deuterium exchangeen_US
dc.subject.keywordmass spectrometryen_US
dc.subject.keywordnuclear magnetic resonance spectroscopyen_US
dc.subject.keywordX-ray crystallographyen_US
dc.titleCoarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Dataen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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