Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.

GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observ...

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Autores principales:	Lars Skjaerven, Barry Grant, Arturo Muga, Knut Teigen, J Andrew McCammon, Nathalie Reuter, Aurora Martinez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4dd297e046af4b9990cbbd9c6db2f83c
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spelling	oai:doaj.org-article:4dd297e046af4b9990cbbd9c6db2f83c2021-11-18T05:50:40ZConformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.1553-734X1553-735810.1371/journal.pcbi.1002004https://doaj.org/article/4dd297e046af4b9990cbbd9c6db2f83c2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423709/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant "opening" of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition.Lars SkjaervenBarry GrantArturo MugaKnut TeigenJ Andrew McCammonNathalie ReuterAurora MartinezPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 3, p e1002004 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Lars Skjaerven Barry Grant Arturo Muga Knut Teigen J Andrew McCammon Nathalie Reuter Aurora Martinez Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
description	GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant "opening" of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition.
format	article
author	Lars Skjaerven Barry Grant Arturo Muga Knut Teigen J Andrew McCammon Nathalie Reuter Aurora Martinez
author_facet	Lars Skjaerven Barry Grant Arturo Muga Knut Teigen J Andrew McCammon Nathalie Reuter Aurora Martinez
author_sort	Lars Skjaerven
title	Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
title_short	Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
title_full	Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
title_fullStr	Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
title_full_unstemmed	Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.
title_sort	conformational sampling and nucleotide-dependent transitions of the groel subunit probed by unbiased molecular dynamics simulations.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4dd297e046af4b9990cbbd9c6db2f83c
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Conformational sampling and nucleotide-dependent transitions of the GroEL subunit probed by unbiased molecular dynamics simulations.

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