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Guiding conformation space search with an all‐atom energy potential
Author(s) -
Brunette TJ,
Brock Oliver
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22123
Subject(s) - maxima and minima , space (punctuation) , search algorithm , energy landscape , energy (signal processing) , computer science , algorithm , mathematical optimization , biological system , mathematics , physics , biology , statistics , mathematical analysis , operating system , thermodynamics
The most significant impediment for protein structure prediction is the inadequacy of conformation space search. Conformation space is too large and the energy landscape too rugged for existing search methods to consistently find near‐optimal minima. To alleviate this problem, we present model‐based search, a novel conformation space search method. Model‐based search uses highly accurate information obtained during search to build an approximate, partial model of the energy landscape. Model‐based search aggregates information in the model as it progresses, and in turn uses this information to guide exploration toward regions most likely to contain a near‐optimal minimum. We validate our method by predicting the structure of 32 proteins, ranging in length from 49 to 213 amino acids. Our results demonstrate that model‐based search is more effective at finding low‐energy conformations in high‐dimensional conformation spaces than existing search methods. The reduction in energy translates into structure predictions of increased accuracy. Proteins 2008. © 2008 Wiley‐Liss, Inc.