K+ versus Na+ ions in a K channel selectivity filter:: A simulation study

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.