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 membranes. Multiple nanosecond-duration molecular dynamics simulations (total simulation time 5 ns) of a bacterial potassium channel (KcsA) embedded in a phospholipid bilayer reveal motions of ions, water, and protein. Comparison of simulations with and without K+ ions indicate that the absence of ions destabilizes the structure of the selectivity filter. Within the selectivity filter, K+ ions interact with the backbone (carbonyl) oxygens, and with the side-chain oxygen of T75. Concerted single-file motions of water molecules and K+ ions within the selectivity filter of the channel occur on a 100-ps time scale. In a simulation with three K+ ions (initially two in the filter and one in the cavity), the ion within the central cavity leaves the channel 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, revealing a favorable site within the otherwise hydrophobically lined cavity. Exit of this ion from the channel is enabled by a transient increase in the diameter of the intracellular mouth. Such "breathing" motions may form the molecular basis of channel gating.