K+/Na+ selectivity in toy cation binding site models is determined by the 'host'.

The macroscopic ion-selective behavior of K(+) channels is mediated by a multitude of physiological factors. However, considering the carbonyl-lined binding site of a conductive K(+) channel as a canonical eightfold coordinated construct can be useful in understanding the principles that correlate the channel's structure with its function. We probe the effects of structure and chemical composition on the K(+)/Na(+) selectivity provided by a variety of simplified droplet-like ion binding site models. We find that when carbonyl- and water-based models capture the qualitative structural features of the K(+) channel binding site, a selective preference for K(+) emerges. Thus our findings suggest that the preference for K(+) over Na(+) exhibited by such models is principally built-in, and is not due to a unique K(+)-selective property of carbonyl functional groups. This suggestion is confirmed by a general thermodynamic assessment, which provides a basis for using simplified models to study the design principles underlying the molecular evolution of K(+) channels.