Multi-stage opening of KcsA potassium channel by targeted molecular dynamics simulation

Determinations of crystal structures of potassium channels provide opportunities to integrate structural and computational studies to resolve the atomic relationship between the structure and the function of potassium channels. The conformational change underlying the gating process of potassium channels is one of the areas have been investigated. However, the dynamic process underlying the conformational changes, which are on a time scale of microsecond, are still obscured. Here targeted molecular dynamics simulations of KcsA K⁺ channel embedded in a solvated lipid bilayer, with the open Kv1.2 structure serving as targeted conformation, are performed to investigate the detailed dynamic opening process. The artificial gating energy is lowered down to the order of that in experimental cases and the running time is up to 150 ns. Thus the channel opens in a multi-stage way. Two stages are observed, each consists of an expanding phase and a quasi-stable phase. It is possible that more stages will exist in a real gating process with much longer time course.