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MolecularStrategies to Achieve Selective Conductancein NaK Channel Variants.

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Title: MolecularStrategies to Achieve Selective Conductancein NaK Channel Variants.
Authors: Wang, Yibo1, Chamberlin, Adam C.1, Noskov, Sergei Yu.1
Source: Journal of Physical Chemistry B. Feb2014, Vol. 118 Issue 8, p2041-2049. 9p.
Subjects: Molecular dynamics, Crystallization, Ion channels, Chemical kinetics, Coordination compounds
Abstract: A recentcrystallization of several ion channels hasprovided strongimpetus for efforts aimed at understanding the different strategiesemployed by nature for selective ion transport. In this work, we usedtwo variants of the selectivity filter of NaK channel to explore molecularmechanisms that give rise to K+-selectivity. We computedone-dimensional (1D) and two-dimensional (2D) potentials of mean force(PMFs) for ion permeation across the channel. The results indicatethat the energies for Na+and K+permeationacross the selectivity filter display significant differences in positionsof the binding sites and barriers. One characteristic signature ofa K+-selective channel is the apparent preservation ofthe site analogous to that of S2 in KcsA. The S2-bound ion can bealmost ideally dehydrated and coordinated by 6 to 8 carbonyls. Ina striking contrast, the PMFs controlling transport of ions in a nonselectivevariant show almost identical profiles for either K+orNa+and significant involvement of water molecules in ioncoordination across the entire selectivity filter. An analysis ofdifferences in 1D PMFs for Na+and K+suggeststhat coordination number alone is an insufficient predictor of siteselectivity, while chemical composition (ratio of carbonyls and watermolecules) correlates well with preference for K+. Multi-ioneffects such as dependence of the barriers and wells for permeantion on the type of copermeant ion were found to play a significantrole in the selectivity signature of the channel as well. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:A recentcrystallization of several ion channels hasprovided strongimpetus for efforts aimed at understanding the different strategiesemployed by nature for selective ion transport. In this work, we usedtwo variants of the selectivity filter of NaK channel to explore molecularmechanisms that give rise to K+-selectivity. We computedone-dimensional (1D) and two-dimensional (2D) potentials of mean force(PMFs) for ion permeation across the channel. The results indicatethat the energies for Na+and K+permeationacross the selectivity filter display significant differences in positionsof the binding sites and barriers. One characteristic signature ofa K+-selective channel is the apparent preservation ofthe site analogous to that of S2 in KcsA. The S2-bound ion can bealmost ideally dehydrated and coordinated by 6 to 8 carbonyls. Ina striking contrast, the PMFs controlling transport of ions in a nonselectivevariant show almost identical profiles for either K+orNa+and significant involvement of water molecules in ioncoordination across the entire selectivity filter. An analysis ofdifferences in 1D PMFs for Na+and K+suggeststhat coordination number alone is an insufficient predictor of siteselectivity, while chemical composition (ratio of carbonyls and watermolecules) correlates well with preference for K+. Multi-ioneffects such as dependence of the barriers and wells for permeantion on the type of copermeant ion were found to play a significantrole in the selectivity signature of the channel as well. [ABSTRACT FROM AUTHOR]
ISSN:15206106
DOI:10.1021/jp4107537