title: Symmetry-restrained molecular dynamics simulations improve homology models of potassium channels.
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. (c) 2009 Wiley-Liss, Inc.
authors.affiliation: Department of Biology, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Andriy
authors.initials: A
authors.lastname: Anishkin
authors.forename: Adina L
authors.initials: AL
authors.lastname: Milac
authors.forename: H Robert
authors.initials: HR
authors.lastname: Guy
mesh_terms: D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015221:Potassium Channels / Q000737:chemistry*; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein
chemical_list: D015221:Potassium Channels