title: Simulations of ion permeation through a potassium channel: molecular dynamics of KcsA in a phospholipid bilayer.
abstract: 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 approximately 900 ps; within the cavity this ion interacts with the Ogamma 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.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
authors.forename: I H
authors.initials: IH
authors.lastname: Shrivastava
authors.forename: M S
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D015221:Potassium Channels; D011510:Proteolipids; C107790:prokaryotic potassium channel; D014867:Water; D011188:Potassium