Simulations of ion permeation through a potassium channel: Molecular dynamics of KcsA in a phospholipid bilayer

Potassium channels enable K+ ions to move passively across biological membr anes. Multiple nanosecond-duration molecular dynamics simulations (total si mulation time 5 ns) of a bacterial potassium channel (KcsA) embedded in a p hospholipid bilayer reveal motions of ions, water, and protein. Comparison of simulations with and without K+ ions indicate that the absence of ions d estabilizes the structure of the selectivity filter. Within the selectivity filter, K+ ions interact with the backbone (carbonyl) oxygens, and with th e side-chain oxygen of T75. Concerted single-file motions of water molecule s and K+ ions within the selectivity filter of the channel occur on a 100-p s time scale. In a simulation with three K+ ions (initially two in the filt er and one in the cavity), the ion within the central cavity leaves the cha nnel via its intracellular mouth after similar to 900 ps, within the cavity this ion interacts with the O gamma atoms of two T107 side chains, reveali ng a favorable site within the otherwise hydrophobically lined cavity. Exit of this ion from the channel is enabled by a transient increase in the dia meter of the intracellular mouth. Such "breathing" motions may form the mol ecular basis of channel gating.