Sodium channels selectively conduct Na+ ions across cellular membrane with extraordinary efficiency, which is essential for initiating action potentials. However, how Na+ ions permeate the ionic channels remains obscure and ambiguous. With more than 40 conductance events from microsecond molecular dynamics simulation, the soft knock-on ion permeation mediated by water molecules was observed and confirmed by the free energy profile and electrostatic potential calculation in this study. During the soft knock-on process, the change of average distance between four oxygen atoms in Glu177-Glu177 plays a very important role for the permeation of Na+ ion. Exploration of the ionic conductance mechanism could provide a guideline for designing ion channel targeted drug.
Keywords: Ion channel; Ion permeation; Molecular dynamics simulation; Potential of mean force; Soft knock-on permeation.
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