(259e) Role of Fluctuations in a Snug-Fit Mechanism of the KcsΑ K+ Channel Selectivity

Biological ion channels are exquisite nano-scale devices that can sort ions with a high fidelity while also conducting them at a high rate. Understanding their mechanism can provide insights into designing, for example, novel separation processes or sensor devices. The KcsA K+ channel is selective for K+ over Na+ at rates of ion transport approaching the diffusion limit. This selectivity is explained thermodynamically in terms of the favorable partitioning of K+ relative to Na+ in a narrow selectivity filter in the channel. We examine the molecular basis for this selectivity by calculating the distribution of binding energies for Na+ and K+ in a simplified model of the filter of the KcsA channel. We find that Na+ binds to the filter with a mean binding energy substantially lower than that for K+. The difference is comparable to the difference in hydration free energies of Na+ and K+ in bulk aqueous solution. Thus, the average filter binding energies do not discriminate Na+ from K+ when measured from a baseline of the difference in bulk hydration free energies. Instead, discrimination can be attributed to the scarcity of favorable binding configurations for Na+ compared to K+. That relative scarcity is quantified as enhanced binding energy fluctuations and is consistent with constriction of the filter induced by Na+ binding.