Andriy Anishkin and Adina L. Milac contributed equally to this work.
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Research Article
Symmetry-restrained molecular dynamics simulations improve homology models of potassium channels
Article first published online: 28 SEP 2009
DOI: 10.1002/prot.22618
Copyright © 2009 Wiley-Liss, Inc.
Issue
Proteins: Structure, Function, and Bioinformatics
Volume 78, Issue 4, pages 932–949, March 2010
Additional Information
How to Cite
Anishkin, A., Milac, A. L. and Guy, H. R. (2010), Symmetry-restrained molecular dynamics simulations improve homology models of potassium channels. Proteins, 78: 932–949. doi: 10.1002/prot.22618
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Andriy Anishkin and Adina L. Milac contributed equally to this work.
Publication History
- Issue published online: 20 JAN 2010
- Article first published online: 28 SEP 2009
- Accepted manuscript online: 28 SEP 2009 12:00AM EST
- Manuscript Accepted: 10 SEP 2009
- Manuscript Revised: 26 AUG 2009
- Manuscript Received: 20 MAY 2009
Funded by
- NIH (Intramural Research Program)
- National Cancer Institute
- Center for Cancer Research
Keywords:
- symmetry annealing;
- ion channels;
- structure prediction;
- structure refinement
Abstract
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.