Thermodynamics and kinetics of ion translocation in the human wild-type and E-1 ' A alpha 7 nicotinic receptor

We use an all-atom model of the human nicotinic acetylcholine receptor alpha 7 in a conductive conformation, to provide the first available mapping of the potential of mean force for the ion translocation across the channel. The modeling is based on MD simulations combined with the milestoning method with Voronoi tessellation. The quality of the protein model and description is confirmed by the agreement with experimental data for proteins of the same family. The specific mutation E-1'A at the cytoplasmatic filter is here shown to strongly affect both sodium and chloride permeation, leading to a complete inversion of selectivity.