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Symmetry‐restrained molecular dynamics simulations improve homology models of potassium channels
Author(s) -
Anishkin Andriy,
Milac Adina L.,
Guy H. Robert
Publication year - 2010
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.22618
Subject(s) - symmetrization , molecular dynamics , homology modeling , stability (learning theory) , biological system , symmetry (geometry) , computer science , rotational symmetry , algorithm , statistical physics , chemistry , physics , computational chemistry , mathematics , geometry , machine learning , mathematical analysis , mechanics , biology , biochemistry , enzyme
Most crystallized homo‐oligomeric ion channels are highly symmetric, which dramatically decreases conformational space and facilitates building homology models (HMs). However, in molecular dynamics (MD) simulations channels deviate from ideal symmetry and accumulate thermal defects, which complicate the refinement of HMs using MD. In this work we evaluate the ability of symmetry constrained MD simulations to improve HMs accuracy, using an approach conceptually similar to Critical Assessment of techniques for protein Structure Prediction (CASP) competition: build HMs of channels with known structure and evaluate the efficiency of proposed methods in improving HMs accuracy (measured as deviation from experimental structure). Results indicate that unrestrained MD does not improve the accuracy of HMs, instantaneous symmetrization improves accuracy but not stability of HMs during subsequent unrestrained MD, while gradually imposing symmetry constraints improves both accuracy (by 5–50%) and stability of HMs. Moreover, accuracy and stability are strongly correlated, making stability a reliable criterion in predicting the accuracy of new HMs. Proteins 2010. © 2009 Wiley‐Liss, Inc.