SOLVATION, WATER PERMEATION, AND IONIC SELECTIVITY OF A PUTATIVE MODEL FOR THE PORE REGION OF THE VOLTAGE-GATED SODIUM-CHANNEL

This paper describes a molecular dynamics and molecular mechanics stud y of the solvation and selectivity of the narrow pore and vestibule re gion of a model-built structure for the voltage-gated sodium channel. The particular structure used was one proposed by Guy and Durell. Howe ver, many of the features we saw would likely be shared with other pos sible models for this channel, such as the one proposed by Lipkind and Fozzard. It was found that the water mobility was reduced in the chan nel and the water orientations were significantly ordered by the chann el environment. Water mobility depended on protein mobility; in a comp uter experiment in which the protein was artificially frozen, channel water at 300 degrees K was immobilized. Water motions were defined in significant part by a series of discrete moves from one pattern of hyd rogen bonding with particular amino acids to another. However, there a re so many different hydrogen bonding patterns that a description of t he motion in terms of transitions among a small number of discrete sta tes is not appropriate. In the model whose solvation we explored, seve ral charged residues seem to play a particularly significant role in d etermining solvation and water motions. Based on energy minimization s tudies, the structure clearly shows selectivity for univalent cations over anions.