A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.

Normal mode analysis (NMA) methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off b...

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Autores principales:	Vincent Frappier, Rafael J Najmanovich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/033ae2d5bb2241dbb2053e8725f9c440
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spelling	oai:doaj.org-article:033ae2d5bb2241dbb2053e8725f9c4402021-11-18T05:52:56ZA coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.1553-734X1553-735810.1371/journal.pcbi.1003569https://doaj.org/article/033ae2d5bb2241dbb2053e8725f9c4402014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24762569/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Normal mode analysis (NMA) methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off between speed and accuracy in different choices. In one extreme one finds accurate but slow molecular-dynamics based methods with all-atom representations and detailed atom potentials. On the other extreme, fast elastic network model (ENM) methods with Cα-only representations and simplified potentials that based on geometry alone, thus oblivious to protein sequence. Here we present ENCoM, an Elastic Network Contact Model that employs a potential energy function that includes a pairwise atom-type non-bonded interaction term and thus makes it possible to consider the effect of the specific nature of amino-acids on dynamics within the context of NMA. ENCoM is as fast as existing ENM methods and outperforms such methods in the generation of conformational ensembles. Here we introduce a new application for NMA methods with the use of ENCoM in the prediction of the effect of mutations on protein stability. While existing methods are based on machine learning or enthalpic considerations, the use of ENCoM, based on vibrational normal modes, is based on entropic considerations. This represents a novel area of application for NMA methods and a novel approach for the prediction of the effect of mutations. We compare ENCoM to a large number of methods in terms of accuracy and self-consistency. We show that the accuracy of ENCoM is comparable to that of the best existing methods. We show that existing methods are biased towards the prediction of destabilizing mutations and that ENCoM is less biased at predicting stabilizing mutations.Vincent FrappierRafael J NajmanovichPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 4, p e1003569 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Vincent Frappier Rafael J Najmanovich A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
description	Normal mode analysis (NMA) methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off between speed and accuracy in different choices. In one extreme one finds accurate but slow molecular-dynamics based methods with all-atom representations and detailed atom potentials. On the other extreme, fast elastic network model (ENM) methods with Cα-only representations and simplified potentials that based on geometry alone, thus oblivious to protein sequence. Here we present ENCoM, an Elastic Network Contact Model that employs a potential energy function that includes a pairwise atom-type non-bonded interaction term and thus makes it possible to consider the effect of the specific nature of amino-acids on dynamics within the context of NMA. ENCoM is as fast as existing ENM methods and outperforms such methods in the generation of conformational ensembles. Here we introduce a new application for NMA methods with the use of ENCoM in the prediction of the effect of mutations on protein stability. While existing methods are based on machine learning or enthalpic considerations, the use of ENCoM, based on vibrational normal modes, is based on entropic considerations. This represents a novel area of application for NMA methods and a novel approach for the prediction of the effect of mutations. We compare ENCoM to a large number of methods in terms of accuracy and self-consistency. We show that the accuracy of ENCoM is comparable to that of the best existing methods. We show that existing methods are biased towards the prediction of destabilizing mutations and that ENCoM is less biased at predicting stabilizing mutations.
format	article
author	Vincent Frappier Rafael J Najmanovich
author_facet	Vincent Frappier Rafael J Najmanovich
author_sort	Vincent Frappier
title	A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
title_short	A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
title_full	A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
title_fullStr	A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
title_full_unstemmed	A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
title_sort	coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/033ae2d5bb2241dbb2053e8725f9c440
work_keys_str_mv	AT vincentfrappier acoarsegrainedelasticnetworkatomcontactmodelanditsuseinthesimulationofproteindynamicsandthepredictionoftheeffectofmutations AT rafaeljnajmanovich acoarsegrainedelasticnetworkatomcontactmodelanditsuseinthesimulationofproteindynamicsandthepredictionoftheeffectofmutations AT vincentfrappier coarsegrainedelasticnetworkatomcontactmodelanditsuseinthesimulationofproteindynamicsandthepredictionoftheeffectofmutations AT rafaeljnajmanovich coarsegrainedelasticnetworkatomcontactmodelanditsuseinthesimulationofproteindynamicsandthepredictionoftheeffectofmutations
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A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.

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