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

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

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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
Article number024701
JournalJournal of Chemical Physics
Volume125
Issue number2
DOIs
StatePublished - 2006
Externally publishedYes

Funding

This work was supported by the US Department of Energy, Contract No. W-7405-ENG-36, under the LDRD program at Los Alamos LA-UR-05-4622. Financial support from the National Science Foundation (CTS-0304062) and the Department of Energy (DE-FG02-04ER25626) is gratefully acknowledged.

FundersFunder number
US Department of Energy
National Science FoundationCTS-0304062
U.S. Department of EnergyDE-FG02-04ER25626
Directorate for Engineering0304062

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