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

Computational and RNA Biology

7 Citations (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.

Original language	English
Journal	Structure
Volume	20
Issue number	6
Pages (from-to)	1028-1039
Number of pages	12
ISSN	0969-2126
DOIs	https://doi.org/10.1016/j.str.2012.03.020
Publication status	Published - 6 Jun 2012

Access to Document

10.1016/j.str.2012.03.020

An efficient null model for conformational fluctuations in proteinsFinal published version, 1.01 MB

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

Cite this

@article{ba31745d9e06469fb00400d5082ab4fa,

title = "An efficient null model for conformational fluctuations in proteins",

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.",

author = "Harder, {Tim Philipp} and Sandro Bottaro and Boomsma, {Wouter Krogh} and Simon Olsson and Jesper Ferkinghoff-Borg and Hamelryck, {Thomas Wim}",

year = "2012",

month = jun,

day = "6",

doi = "10.1016/j.str.2012.03.020",

language = "English",

volume = "20",

pages = "1028--1039",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - An efficient null model for conformational fluctuations in proteins

AU - Harder, Tim Philipp

AU - Bottaro, Sandro

AU - Boomsma, Wouter Krogh

AU - Olsson, Simon

AU - Ferkinghoff-Borg, Jesper

AU - Hamelryck, Thomas Wim

PY - 2012/6/6

Y1 - 2012/6/6

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.

U2 - 10.1016/j.str.2012.03.020

DO - 10.1016/j.str.2012.03.020

M3 - Journal article

SN - 0969-2126

VL - 20

SP - 1028

EP - 1039

JO - Structure

JF - Structure

IS - 6

ER -

An efficient null model for conformational fluctuations in proteins

Abstract

Access to Document

Fingerprint

Cite this