RT Journal Article SR Electronic T1 Exploring the Complex Dynamics of an Ion Channel Voltage Sensor Domain via Computation JF bioRxiv FD Cold Spring Harbor Laboratory SP 108217 DO 10.1101/108217 A1 Lucie Delemotte A1 Marina A. Kasimova A1 Daniel Sigg A1 Michael L. Klein A1 Vincenzo Carnevale A1 Mounir Tarek YR 2017 UL http://biorxiv.org/content/early/2017/02/16/108217.abstract AB Voltage-gated ion channels are ubiquitous proteins that orchestrate electrical signaling across excitable membranes. Key to their function is activation of the voltage sensor domain (VSD), a transmembrane four alpha-helix bundle that triggers channel opening. Modeling of currents from electrophysiology experiments yields a set of kinetic parameters for a given channel, but no direct molecular insight. Here we use molecular dynamics (MD) simulations to determine the free energy landscape of VSD activation and to, ultimately, predict the time evolution of the resulting gating currents. Our study provides the long-sought-for bridge between electrophysiology and microscopic molecular dynamics and confirms, as already suggested on the basis of experiments, that rate-limiting barriers play a critical role in activation kinetics.