Distinct interactions of Na+ and Ca2+ ions with the selectivity filter of the bacterial sodium channel NaVAb

abstract Rapid and selective ion transport is essential for the generation and regulation of electrical signalingpathways in living organisms. In this study, we use molecular dynamics simulations and free energy cal-culations to investigate how the bacterial sodium channel Na V Ab (Arcobacter butzleri) differentiatesbetween Na + and Ca 2+ ions. Multiple nanosecond molecular dynamics simulations revealed distinct bind-ing patterns for these two cations in the selectivity filter and suggested a high affinity calcium bindingsite formed by backbone atoms of residues Leu-176 and Thr-175 (S CEN ) in the sodium channel selectivityfilter. 2012 Elsevier Inc. All rights reserved. 1. IntroductionNa + flux is vital for initiating action potentials in the mem-branes of most electrically excitable cells [1]. Recent homotetra-meric crystal structures of bacterial Na V channels [2–5] providenew possibilities for investigating the molecular basis of ion selec-tivity and transport in these channels. The mechanisms of howthese channels discriminate between different ion types are poorlyunderstood. Recent molecular dynamics investigations [6,7] pro-vide insights into Na