Figure 8. Molecular dynamics of sodium conductance.

Entry and exit of sodium ions in the pore of Na_VAb were analyzed without constraints for 23 µs at 150 mM Na⁺ and V=0. A. Axial distribution of Na⁺ in the selectivity filter (SF) and central cavity (CC), distinguishing between states in which Na⁺ is directly bound to Glu177 (“E”, green), to both Glu177 and Leu176 (“EL”, yellow), or to neither (brown). The selectivity filter is defined by two spatially resolved Na⁺ binding sites, E and EL. The small peaks at z = −0.65 and z = 0.40 nm in the brown distribution correspond to direct Na⁺ coordination by the hydroxyl O atom of Ser178 and water-mediated coordination to the carbonyl O atom of Thr175, respectively. B. Mechanism and kinetics of Na⁺ translocation through the selectivity filter. The black box represents the selectivity filter, with the central cavity to the right below and the extracellular mouth to the left. The populations of all four states 1’, 2, 2’, and 3, which differ in the occupancy of the channel and of the selectivity filter, are shown in %, and the rate constants computed from the molecular dynamics trajectories are shown above or below each arrow in units of µs⁻¹. At this ionic concentration (150 mM), states 2 and 2’ correspond to the resting state of the system. The exchange between states 2 and 2’, which corresponds to a unitary ionic translocation through the selectivity filter, involves either one-ion or three-ion intermediate states (Chakrabarti et al., 2013).