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: 1.9). 01/2010; 485(1-3):1-7. DOI: 10.1016/j.cplett.2009.12.013
Source: PubMed


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.

Download full-text


Available from: Susan B Rempe, Oct 30, 2015
  • Source
    • "The background literature (Allen et al., 2000; Luzhkov and Åqvist, 2001; Zhou et al., 2001; Shrivastava et al., 2002; Correspondence to Dilip Asthagiri: dilipa@­ 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. "

    The Journal of General Physiology 05/2011; 137(5):427-33. DOI:10.1085/jgp.201010533 · 4.79 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The functional mechanism of the F1Fo ATP synthase, like many membrane transporters and pumps, entails a conformational cycle that is coupled to the movement of H+ or Na+ ions across its transmembrane domain, down an electrochemical gradient. This coupling is an efficient means of energy transduction and regulation, provided that ion binding to the membrane domain, known as Fo, is appropriately selective. In this study we set out to establish the structural and energetic basis for the ion-binding selectivity of the membrane-embedded Fo rotors of two representative ATP synthases. First, we use a biochemical approach to demonstrate the inherent binding selectivity of these rotors, that is, independently from the rest of the enzyme. We then use atomically detailed computer simulations of wild-type and mutagenized rotors to calculate and rationalize their selectivity, on the basis of the structure, dynamics and coordination chemistry of the binding sites. We conclude that H+ selectivity is most likely a robust property of all Fo rotors, arising from the prominent presence of a conserved carboxylic acid and its intrinsic chemical propensity for protonation, as well as from the structural plasticity of the binding sites. In H+-coupled rotors, the incorporation of hydrophobic side chains to the binding sites enhances this inherent H+ selectivity. Size restriction may also favor H+ over Na+, but increasing size alone does not confer Na+ selectivity. Rather, the degree to which Fo rotors may exhibit Na+ coupling relies on the presence of a sufficient number of suitable coordinating side chains and/or structural water molecules. These ligands accomplish a shift in the relative binding energetics, which under some physiological conditions may be sufficient to provide Na+ dependence.
    Biochimica et Biophysica Acta 04/2010; 1797(6-7):763-72. DOI:10.1016/j.bbabio.2010.04.014 · 4.66 Impact Factor
  • Source
    Rempe · Susan B ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Affordable clean water is both a global and a national security issue as lack of it can cause death, disease, and international tension. Furthermore, efficient water filtration reduces the demand for energy, another national issue. The best current solution to clean water lies in reverse osmosis (RO) membranes that remove salts from water with applied pressure, but widely used polymeric membrane technology is energy intensive and produces water depleted in useful electrolytes. Furthermore incremental improvements, based on engineering solutions rather than new materials, have yielded only modest gains in performance over the last 25 years. We have pursued a creative and innovative new approach to membrane design and development for cheap desalination membranes by approaching the problem at the molecular level of pore design. Our inspiration comes from natural biological channels, which permit faster water transport than current reverse osmosis membranes and selectively pass healthy ions. Aiming for an order-of-magnitude improvement over mature polymer technology carries significant inherent risks. The success of our fundamental research effort lies in our exploiting, extending, and integrating recent advances by our team in theory, modeling, nano-fabrication and platform development. A combined theoretical and experimental platform has been developed to understand the interplay between water flux and ion rejection in precisely-defined nano-channels. Our innovative functionalization of solid state nanoporous membranes with organic protein-mimetic polymers achieves 3-fold improvement in water flux over commercial RO membranes and has yielded a pending patent and industrial interest. Our success has generated useful contributions to energy storage, nanoscience, and membrane technology research and development important for national health and prosperity.
Show more