Influence of interionic interactions on functional state and blocker binding of voltage-gated potassium channels

Abstract

A mechanism of ion conduction of a voltagegated potassium channel KcsA was investigated in fullatomic approximation at a trajectory length of 100 ns using the Lomonosov supercomputer. Methods of molecular dynamics were employed. A structure of the KcsA channel in the open state obtained by Xray structure analysis (PDB ID 3fb7) was used. Free energy profiles of the KcsA pore occupied with either one or three potassium ions were calculated. It was shown that, under physiological conditions, ions pass through the channel pore cooperatively and the mechanism most probably includes three ions permeating in concert. Interactions of the mammalian voltagegated channel Kv 1.2 with neurotoxin were investigated. It was dem� onstrated that the effect of interionic interactions on binding of a blocker is rather insufficient.