Modeling of Ion Permeation in Calcium and Sodium Channel Selectivity Filters

Ganesh, Raj PS and Chanda, Baron and Gupta, SK and Mathew, MK and Chandrasekhar, Jayaraman (2000) Modeling of Ion Permeation in Calcium and Sodium Channel Selectivity Filters. In: Proteins: Structure, Function, and Genetics, 38 (4). pp. 384-392.

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Abstract

Structure function studies have shown that it is possible to convert a sodium channel to a calcium-selective channel by a single amino acid substitution in the selectivity filter locus. Ion permeation through the "model selectivity filter" wasmodeled with a reduced set of functional groups representative of the constituent amino acid side chains. Force-field minimizations were conducted to obtain the energy profile of the cations as they get desolvated and bind to the "model selectivity filter". The calculations suggest that the ion selectivity in the calcium channel is due to preferential binding, whereas in the sodium channel it is due to exclusion. Energetics of displacement of a bound cation from the calcium "model selectivity filter" by another cation suggest that "multi-ion mechanism" reduces the activation barrier for ion permeation. Thus, the simple model captures qualitatively most of the conduction characteristics of sodium and calcium channels. However, the computed barriers for permeation are fairly large, suggesting that ion interaction with additional residues along the transport path may be essential to effect desolvation.

Item Type:	Journal Article
Publication:	Proteins: Structure, Function, and Genetics
Publisher:	Wiley-Liss, Inc.
Additional Information:	The copyright belongs to Wiley-Liss, Inc.
Keywords:	minimizations;single ion;multi ion;binding;energetics;solvation
Department/Centre:	Division of Mechanical Sciences > Chemical Engineering Division of Chemical Sciences > Organic Chemistry
Date Deposited:	19 Jul 2005
Last Modified:	19 Sep 2010 04:19
URI:	http://eprints.iisc.ac.in/id/eprint/3331

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