Biophys J, February 2000, p. 557-570, Vol. 78, No. 2

Simulations of Ion Permeation Through a Potassium Channel: Molecular Dynamics of KcsA in a Phospholipid Bilayer

Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom

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 ~900 ps; within the cavity this ion interacts with the O 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.

Biophys J, February 2000, p. 557-570, Vol. 78, No. 2
© 2000 by the Biophysical Society   0006-3495/00/02/557/14  $2.00

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