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An Efficient Null Model for Conformational Fluctuations in Proteins

Harder, Tim; Borg, Mikael; Bottaro, Sandro; Boomsma, Wouter LU ; Olsson, Simon; Ferkinghoff-Borg, Jesper and Hamelryck, Thomas (2012) In Structure 20(6). p.1028-1039
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Structure
volume
20
issue
6
pages
1028 - 1039
publisher
Cell Press
external identifiers
  • wos:000305094500011
  • scopus:84861988477
ISSN
0969-2126
DOI
10.1016/j.str.2012.03.020
language
English
LU publication?
yes
id
0e149042-e7b7-4189-9183-5c6f513d43ca (old id 2895932)
date added to LUP
2012-07-24 11:31:17
date last changed
2017-10-01 03:12:16
@article{0e149042-e7b7-4189-9183-5c6f513d43ca,
  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 and Borg, Mikael and Bottaro, Sandro and Boomsma, Wouter and Olsson, Simon and Ferkinghoff-Borg, Jesper and Hamelryck, Thomas},
  issn         = {0969-2126},
  language     = {eng},
  number       = {6},
  pages        = {1028--1039},
  publisher    = {Cell Press},
  series       = {Structure},
  title        = {An Efficient Null Model for Conformational Fluctuations in Proteins},
  url          = {http://dx.doi.org/10.1016/j.str.2012.03.020},
  volume       = {20},
  year         = {2012},
}