Shrivastava I H, Sansom M S
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Biophys J. 2000 Feb;78(2):557-70. doi: 10.1016/S0006-3495(00)76616-1.
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.
钾通道能使钾离子被动穿过生物膜。对嵌入磷脂双分子层的细菌钾通道（KcsA）进行多次纳秒时长的分子动力学模拟（总模拟时间5纳秒），揭示了离子、水和蛋白质的运动情况。有钾离子和无钾离子的模拟结果对比表明，没有离子会使选择性过滤器的结构不稳定。在选择性过滤器内，钾离子与主链（羰基）氧原子以及T75的侧链氧原子相互作用。通道选择性过滤器内水分子和钾离子的协同单排运动发生在100皮秒的时间尺度上。在有三个钾离子的模拟中（最初两个在过滤器中，一个在腔中），中央腔内的离子在大约900皮秒后通过其细胞内口离开通道；在腔内，该离子与两个T107侧链的Oγ原子相互作用，揭示了在原本疏水内衬的腔内的一个有利位点。该离子从通道的流出是由细胞内口直径的短暂增加实现的。这种“呼吸”运动可能构成通道门控的分子基础。
