Molecular Dynamics Simulation Approaches to K Channels: Conformational Flexibility and Physiological Function

Molecular modeling and simulations enable extrapolation for the structure of bacterial potassium channels to the function of their mammalian homologues. Molecular dynamics simulations have revealed the concerted single-file motion of potassium ions and water molecules through the selectivity filter of K channels and the role of filter flexibility in ion permeation and in "fast gating." Principal components analysis of extended K channel simulations suggests that hinge-bending of pore-lining M2 (or S6) helices plays a key role in K channel gating. Based on these and other simulations, a molecular model for gating of inward rectifier K channel gating is presented.