Microsecond molecular dynamics simulations of the open state structure of a bacterial voltage-gated sodium channel reveal mechanisms of ion selectivity and conduction

Microsecond atomic detail equilibrium molecular dynamics simulations based on the open-state crystal structure (McCusker et al, 2012, Nature Comm) of a bacterial voltage-gated sodium channel (NavMs) have been employed to characterize the mechanisms underlying ion selectivity and conductance of the channel embedded in a lipid bilayer membrane. This approach captured the full plethora of conduction events, revealing a complex mixture of single and multi-ion phenomena, with decoupled rapid bi-directional water transport. Channel selectivity for Na over K ions was found to increase with decreasing applied membrane potential. In marked difference to K-channel simulations, no voltage lag was observed for Na+. Unlike in K+ channels, the ions are fully hydrated at all times, even when bound. The ion positions were correlated with electron density in selectivity filter of the crystal structure. Remarkably, and in stark contrast to K-channels, ionic conduction was found to be independent of net water flux, which was zero for all applied voltages and ionic species. This zero water transport was found to result from the balance of two large and opposing water fluxes of equal magnitude