Ion dynamics and selectivity of Na_v channels from molecular dynamics simulation

The voltage-gated sodium (Na_v) channels are crucial in initiating and propagating action potentials in excitable cells. In this work, with atomistic molecular simulations employing conventional and advanced sampling techniques, we investigate the dynamics of a series of Na_v channels. The thermodynamic picture along the ion permeation pathway is obtained and the ion dynamics in the channels are analyzed. The ion permeation pathway could be divided into several regions. The cation enters the channel through the selectivity filter, stays in the global free energy minimum at the central cavity, and waits for the open of the activation gate. Exchanges between neighboring ions are also observed. There is an obvious free energy barrier for K⁺ entering the channel, and the thermodynamic stability of K⁺ in the central cavity is similar to the extracellular side, while there is no explicit barrier for Na⁺ and the cation is more stable in the cavity.