Tools for channels: moving towards molecular calculations of gating and permeation in ion channel biophysics.
Recent X-ray structures of voltage gated potassium channels provide an exciting opportunity to connect molecular structures with measured biological function. Two of the most important connections for these channels are: first, to the molecular basis behind selectivity and the associated free energy profile underlying ionic current flow and, second, to a true molecular understanding of the large-scale conformational transitions that underlie voltage dependent gating. But, existing computational tools need to be further developed to reach these goals. In this contribution to the symposia on sampling methods we outline our dynamic importance sampling method for sampling large-scale conformational transitions as well as our studies with non-equilibrium work events and equilibrium overlap sampling (OS) methods for sampling events related to the calculation of relative free energies.
Woolf
Thomas B
TB
Department of Physiology, Johns Hopkins University, School of Medicine, Biophysics 206, 725 N. Wolfe Street, Baltimore, MD 21205, USA. woolf@groucho.med.jhmi.edu
Zuckerman
Daniel M
DM
Lu
Nandou
N
Jang
Hyunbum
H
D000465:Algorithms; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D019295:Computational Biology; D018360:Crystallography, X-Ray; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry; D013816:Thermodynamics
D007473:Ion Channels; D015221:Potassium Channels