Molecular Dynamics Study of Ion Conduction and Selectivity in a Prokaryotic Ion Channel

Abstract

Since the publication of crystal structure of NavAb, the first of a (prokaryotic) voltage gated sodium channel, several computational studies have been aimed at determining the mechanisms of ion selectivity and ion conduction in voltage gated sodium channels. We provide a two-part study, well-converged free energy surfaces involving one, two and three ions provide results consistent with microsecond timescale simulations of ion conduction over concentration and voltages. The position of ions in the pore and cavity correlate to coordination number and side chain orientation, showing, as suggested by Chakrabarti et al. (PNAS (2013) 110, 11331). More surprising, presence of an ion in the aqueous cavity beneath the selectivity filter was sufficient to influence glutamate conformation.Because the crystal structure of NavAb was in a closed pore conformation, we truncated the S5 and S6 helices and restrained these outer helices harmonically in a membrane represented by supporting lattice of neon. The turrets, pore helices and selectivity filter were free to move. Conductances were in the range of the experimental values; however, our studies show no preference for sodium conduction over potassium conduction at physiological conditions (−200mV, 0.15 M salt). While sodium conductance varied little with respect to concentration and presence of potassium in solution, stronger potassium selectivity is observed at 1 M and in mixed solutions. Our results are consistent with the observation of anomalous mole fraction effect in NaChBac by Finol-Urdaneta et al. (JGP (2014) 143, 157-171), though not sufficient to confirm such an effect. Additionally, we provide mechanisms for ion conduction showing a greater variety of states and transitions occupied during potassium conduction, and note that at higher concentrations of salt the mechanism of conduction is not as clearly cut.