Shrivastava Indira H, Tieleman D Peter, Biggin Philip C, Sansom Mark S P
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Biophys J. 2002 Aug;83(2):633-45. doi: 10.1016/s0006-3495(02)75197-7.
Molecular dynamics simulations of a bacterial potassium channel (KcsA) embedded in a phospholipid bilayer reveal significant differences in interactions of the selectivity filter with K(+) compared with Na(+) ions. K(+) ions and water molecules within the filter undergo concerted single-file motion in which they translocate between adjacent sites within the filter on a nanosecond timescale. In contrast, Na(+) ions remain bound to sites within the filter and do not exhibit translocation on a nanosecond timescale. Furthermore, entry of a K(+) ion into the filter from the extracellular mouth is observed, whereas this does not occur for a Na(+) ion. Whereas K(+) ions prefer to sit within a cage of eight oxygen atoms of the filter, Na(+) ions prefer to interact with a ring of four oxygen atoms plus two water molecules. These differences in interactions in the selectivity filter may contribute to the selectivity of KcsA for K(+) ions (in addition to the differences in dehydration energy between K(+) and Na(+)) and the block of KcsA by internal Na(+) ions. In our simulations the selectivity filter exhibits significant flexibility in response to changes in ion/protein interactions, with a somewhat greater distortion induced by Na(+) than by K(+) ions.
嵌入磷脂双分子层的细菌钾通道（KcsA）的分子动力学模拟显示，与钠离子相比，选择性过滤器与钾离子相互作用存在显著差异。过滤器内的钾离子和水分子经历协同单排运动，它们在纳秒时间尺度内在过滤器内相邻位点之间迁移。相比之下，钠离子仍与过滤器内的位点结合，在纳秒时间尺度上不发生迁移。此外，观察到钾离子从细胞外口进入过滤器，而钠离子则不会发生这种情况。钾离子倾向于位于过滤器八个氧原子构成的笼中，而钠离子则倾向于与四个氧原子加两个水分子组成的环相互作用。选择性过滤器中这些相互作用的差异可能有助于KcsA对钾离子的选择性（除了钾离子和钠离子脱水能的差异之外）以及内部钠离子对KcsA的阻断。在我们的模拟中，选择性过滤器对离子/蛋白质相互作用的变化表现出显著的灵活性，钠离子引起的扭曲比钾离子略大。
