Abstract
Known structures of selective ion channels share a common property: a narrow constriction, presumably crucial for ionic discrimination. This region can be fairly long, imposing single file motion on waters and ion(s). We apply the semi-microscopic Monte Carlo approach to study permeation in the KcsA channel, decomposing energetics into a three-step process: cation dehydration; ion transfer into a uniform low epsilon dielectric; and transfer from the uniform dielectric into the channel. The influence of individual channel structural features is separately assessed. The aqueous cavity has only a modest stabilizing effect on nearby ions in the filter. Ionic solvation in the filter reflects the combined influence of the single file waters, the binding pockets' carbonyls, the alpha helices directed at the cavity and the negative residues near the extracellular surface of the channel; no one feature dominates. At all sites along the permeation pathway there is substantial discrimination favouring K+ over Na+; conversely, there is little discrimination among the larger alkali cations. Selectivity for K+ over Na+ appears due to the inability of the filter's carbonyl oxygens to ideally coordinate Na+.