An efficient null model for conformational fluctuations in proteins

Tim Philipp Harder; Sandro Bottaro; Wouter Krogh Boomsma; Simon Olsson; Jesper Ferkinghoff-Borg; Thomas Wim Hamelryck

doi:10.1016/j.str.2012.03.020

An efficient null model for conformational fluctuations in proteins

Tim Philipp Harder, Sandro Bottaro, Wouter Krogh Boomsma, Simon Olsson, Jesper Ferkinghoff-Borg, Thomas Wim Hamelryck

Bioinformatik og RNA Biologi

7 Citationer (Scopus)

Abstract

Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins.

Originalsprog	Engelsk
Tidsskrift	Structure
Vol/bind	20
Udgave nummer	6
Sider (fra-til)	1028-1039
Antal sider	12
ISSN	0969-2126
DOI	https://doi.org/10.1016/j.str.2012.03.020
Status	Udgivet - 6 jun. 2012

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10.1016/j.str.2012.03.020

An efficient null model for conformational fluctuations in proteinsForlagets udgivne version, 1,01 MB

http://www.cell.com/article/S0969212612001396/pdf

Citationsformater

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AU - Harder, Tim Philipp

AU - Bottaro, Sandro

AU - Boomsma, Wouter Krogh

AU - Olsson, Simon

AU - Ferkinghoff-Borg, Jesper

AU - Hamelryck, Thomas Wim

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N2 - Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins.

AB - Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins.

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DO - 10.1016/j.str.2012.03.020

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An efficient null model for conformational fluctuations in proteins

Abstract

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