Role of fluctuations in a snug-fit mechanism of KcsA channel selectivity

D. Asthagiri, Lawrence R. Pratt, Michael E. Paulaitis

Research output: Contribution to journalArticlepeer-review

Abstract

The thermodynamic exclusion of Na + relative to K + in potassium channels is examined by calculating the distribution of binding energies for Na + and K + in a model of the selectivity filter of the KcsA potassium channel. These distributions are observed to take a surprisingly simple form: Gaussian with a slight positive skewness that is insignificant in the present context. Complications that might be anticipated from these distributions are not problematic here. Na + occupies the filter with a mean binding energy substantially lower than that of K +. The difference is comparable to the difference in hydration free energies of Na + and K + in bulk aqueous solution. Thus, the average energies of binding to the filter do not discriminate Na + from K + when measured from a baseline of the difference in bulk hydration free energies. The strong binding of Na + constricts the filter, consistent with a negative partial molar volume of Na + in water in contrast with 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 + compared to K +. That relative scarcity is quantified as enhanced binding energy fluctuations, which reflects both the energetically stronger binding of Na + and the constriction of the filter induced by Na + binding.

Original languageEnglish (US)
Article number024701
JournalJournal of Chemical Physics
Volume125
Issue number2
DOIs
StatePublished - 2006
Externally publishedYes

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

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