Berlin 2008 – scientific programme

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SYMP: Symposium Computational Soft matter physics

SYMP 1: Computational soft matter physics

SYMP 1.6: Invited Talk

Thursday, February 28, 2008, 11:45–12:15, H 0105

Role of fluctuations in the selectivity mechanism for the KcsA potassium channel — •Michael E. Paulaitis¹, Dilip Asthagiri², and Lawrence R. Pratt³ — ¹Department of Chemical and Biomolecular Engineering, Ohio State University — ²Department of Chemical and Biomolecular Engineering, Johns Hopkins University — ³Department of Chemical and Biomolecular Engineering, Tulane University

The KcsA potassium channel belongs to a class of channels that is selective for K⁺ over Na⁺ at rates of K⁺ transport approaching the diffusion limit. Selectivity is explained thermodynamically in terms of the favorable partitioning of K⁺ relative to Na⁺ in a narrow selectivity filter in the channel. One mechanism for this selectivity invokes the size difference between K⁺ and Na⁺, and the molecular complementarity of the selectivity filter with the larger K⁺ ion. An alternative view holds that size-based selectivity is precluded because the conformational fluctuations of the selectivity filter are greater than the size difference between these two ions. A quasi-chemical theory implemented on the basis of molecular simulation is derived to examine these hypotheses by calculating the distribution of binding energies for Na⁺ and K⁺ in a model of the selectivity filter of the KcsA channel. We find that Na⁺ binds strongly to the selectivity filter with a mean binding energy substantially more favorable 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 the baseline of the difference in bulk hydration free energies. Strong binding of the smaller Na⁺ also constricts the selectivity filter, consistent with a negative partial molar volume of Na⁺ in water in contrast to a positive partial molar volume of K⁺ in water. Discrimination in favor of K⁺ can be attributed to the scarcity of favorable binding configurations for Na⁺ relative to K⁺. That relative scarcity is quantified as enhanced binding energy fluctuations, which reflect both the energetically stronger binding of Na⁺ and the constriction of the filter induced by Na⁺ binding.