Cargando…
Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics
The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or on their ability to perform wider and sometimes highly elaborated motions. Hence, there is considerable interest in the definition of accurate coarse-grained des...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757084/ https://www.ncbi.nlm.nih.gov/pubmed/24009495 http://dx.doi.org/10.1371/journal.pcbi.1003209 |
_version_ | 1782282172421373952 |
---|---|
author | Dehouck, Yves Mikhailov, Alexander S. |
author_facet | Dehouck, Yves Mikhailov, Alexander S. |
author_sort | Dehouck, Yves |
collection | PubMed |
description | The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or on their ability to perform wider and sometimes highly elaborated motions. Hence, there is considerable interest in the definition of accurate coarse-grained descriptions of protein dynamics, as an alternative to more computationally expensive approaches. In particular, the elastic network model, in which residue motions are subjected to pairwise harmonic potentials, is known to capture essential aspects of conformational dynamics in proteins, but has so far remained mostly phenomenological, and unable to account for the chemical specificities of amino acids. We propose, for the first time, a method to derive residue- and distance-specific effective harmonic potentials from the statistical analysis of an extensive dataset of NMR conformational ensembles. These potentials constitute dynamical counterparts to the mean-force statistical potentials commonly used for static analyses of protein structures. In the context of the elastic network model, they yield a strongly improved description of the cooperative aspects of residue motions, and give the opportunity to systematically explore the influence of sequence details on protein dynamics. |
format | Online Article Text |
id | pubmed-3757084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37570842013-09-05 Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics Dehouck, Yves Mikhailov, Alexander S. PLoS Comput Biol Research Article The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or on their ability to perform wider and sometimes highly elaborated motions. Hence, there is considerable interest in the definition of accurate coarse-grained descriptions of protein dynamics, as an alternative to more computationally expensive approaches. In particular, the elastic network model, in which residue motions are subjected to pairwise harmonic potentials, is known to capture essential aspects of conformational dynamics in proteins, but has so far remained mostly phenomenological, and unable to account for the chemical specificities of amino acids. We propose, for the first time, a method to derive residue- and distance-specific effective harmonic potentials from the statistical analysis of an extensive dataset of NMR conformational ensembles. These potentials constitute dynamical counterparts to the mean-force statistical potentials commonly used for static analyses of protein structures. In the context of the elastic network model, they yield a strongly improved description of the cooperative aspects of residue motions, and give the opportunity to systematically explore the influence of sequence details on protein dynamics. Public Library of Science 2013-08-29 /pmc/articles/PMC3757084/ /pubmed/24009495 http://dx.doi.org/10.1371/journal.pcbi.1003209 Text en © 2013 Dehouck, Mikhailov http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dehouck, Yves Mikhailov, Alexander S. Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title | Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title_full | Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title_fullStr | Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title_full_unstemmed | Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title_short | Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics |
title_sort | effective harmonic potentials: insights into the internal cooperativity and sequence-specificity of protein dynamics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757084/ https://www.ncbi.nlm.nih.gov/pubmed/24009495 http://dx.doi.org/10.1371/journal.pcbi.1003209 |
work_keys_str_mv | AT dehouckyves effectiveharmonicpotentialsinsightsintotheinternalcooperativityandsequencespecificityofproteindynamics AT mikhailovalexanders effectiveharmonicpotentialsinsightsintotheinternalcooperativityandsequencespecificityofproteindynamics |