Density functional theory investigations on the chemical basis of the selectivity filter in the K+ channel protein.

The chemical-physical basis of loading and release of K(+) and Na(+) ions in and out of the selectivity filter of the K(+) channel has been investigated using the B3LYP method of density functional theory. We have shown that the difference between binding free energies of K(+) and Na(+) to the cavity end of the filter is smaller than the difference between the K(+) and Na(+) solvation free energies. Thus, the loading of K(+) ions into the cavity end of the selectivity filter from the solution phase is suggested to be selective prior to the subsequent conduction process. It is shown that the extracellular end of the filter is only optimal for K(+) ions, because K(+) ions prefer the coordination environment of eight carbonyl oxygens. Na(+) ions do not fit into the extracellular end of the filter, since they prefer the coordination environment of six carbonyl oxygens. Overall, the results suggest that the rigid C(4) symmetric selectivity filter is specifically designed for conduction of K(+) ions.