Article

Ion selectivity from local configurations of ligands in solutions and ion channels

Department of Chemical and Biomolecular Engineering and Institute of NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Chemical Physics Letters (Impact Factor: 1.99). 01/2010; 485(1-3):1-7. DOI: 10.1016/j.cplett.2009.12.013
Source: PubMed

ABSTRACT Probabilities of numbers of ligands proximal to an ion lead to simple, general formulae for the free energy of ion selectivity between different media. That free energy does not depend on the definition of an inner shell for ligand-counting, but other quantities of mechanistic interest do. If analysis is restricted to a specific coordination number, then two distinct probabilities are required to obtain the free energy in addition. The normalizations of those distributions produce partition function formulae for the free energy. Quasi-chemical theory introduces concepts of chemical equilibrium, then seeks the probability that is simplest to estimate, that of the most probable coordination number. Quasi-chemical theory establishes the utility of distributions of ligand-number, and sharpens our understanding of quasi-chemical calculations based on electronic structure methods. This development identifies contributions with clear physical interpretations, and shows that evaluation of those contributions can establish a mechanistic understanding of the selectivity in ion channels.

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    • "The background literature (Allen et al., 2000; Luzhkov and Åqvist, 2001; Zhou et al., 2001; Shrivastava et al., 2002; Correspondence to Dilip Asthagiri: dilipa@­jhu.edu MacKinnon, 2003; Noskov et al., 2004; Asthagiri et al., 2006, 2010; Noskov and Roux, 2006, 2007; Bostick and Brooks, 2007, 2009; Lockless et al., 2007; Thomas et al., 2007; Varma and Rempe, 2007, 2008; Miloshevsky and Jordan, 2008; Varma et al., 2008; Dixit et al., 2009; Roux, 2010; Dixit and Asthagiri, 2011) and the other articles in this series can be consulted to gain some appreciation for the vibrant discussions on selectivity. We aim for a pedagogical approach here. "
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    • "A distinct glutamate side chain, conserved across all c-subunits of F-ATP synthases (sometimes substituted by aspartate), appears to play a prominent role in ion coordination. A number of factors may contribute to the ion selectivity in a protein binding site, including its size, coordination number and type of ligands, as well as the relative hydration free energies of the ions involved [24] [25] [26] [27] [28] [29] [30] [31]. In the case of protonation, the intrinsic pK a of the ionizable groups involved must also be considered. "
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