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Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data
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. How...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344923/ https://www.ncbi.nlm.nih.gov/pubmed/28344973 http://dx.doi.org/10.3389/fmolb.2017.00013 |
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author | Devaurs, Didier Antunes, Dinler A. Papanastasiou, Malvina Moll, Mark Ricklin, Daniel Lambris, John D. Kavraki, Lydia E. |
author_facet | Devaurs, Didier Antunes, Dinler A. Papanastasiou, Malvina Moll, Mark Ricklin, Daniel Lambris, John D. Kavraki, Lydia E. |
author_sort | Devaurs, Didier |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5344923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53449232017-03-24 Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data Devaurs, Didier Antunes, Dinler A. Papanastasiou, Malvina Moll, Mark Ricklin, Daniel Lambris, John D. Kavraki, Lydia E. Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2017-03-10 /pmc/articles/PMC5344923/ /pubmed/28344973 http://dx.doi.org/10.3389/fmolb.2017.00013 Text en Copyright © 2017 Devaurs, Antunes, Papanastasiou, Moll, Ricklin, Lambris and Kavraki. http://creativecommons.org/licenses/by/4.0/ This 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. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Devaurs, Didier Antunes, Dinler A. Papanastasiou, Malvina Moll, Mark Ricklin, Daniel Lambris, John D. Kavraki, Lydia E. Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title | Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title_full | Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title_fullStr | Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title_full_unstemmed | Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title_short | Coarse-Grained Conformational Sampling of Protein Structure Improves the Fit to Experimental Hydrogen-Exchange Data |
title_sort | coarse-grained conformational sampling of protein structure improves the fit to experimental hydrogen-exchange data |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344923/ https://www.ncbi.nlm.nih.gov/pubmed/28344973 http://dx.doi.org/10.3389/fmolb.2017.00013 |
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