Journal article
An Efficient Null Model for Conformational Fluctuations in Proteins
Niels Bohr Institute1
University of Copenhagen2
Department of Informatics and Mathematical Modeling, Technical University of Denmark3
Department of Electrical Engineering, Technical University of Denmark4
Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark5
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.
Language: | English |
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Year: | 2012 |
Pages: | 1028-1039 |
ISSN: | 18784186 and 09692126 |
Types: | Journal article |
DOI: | 10.1016/j.str.2012.03.020 |
ORCIDs: | 0000-0002-3927-7897 and 0000-0003-2917-3602 |
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