Biology is built around the chemistry of charged macromolecules functioning in an aqueous medium. Inorganic ions in the medium not only confer electroneutrality to the system but, by virtue of their strong interaction with the solvent and the biomaterial, also play specific functional roles as well. A particularly clear example is seen in the observed asymmetrical distribution of Na+ and K+ across the cell membrane. Cells use ion specific channels and exploit this asymmetry in generating nerve impulses. Such ion-protein interactions are but a manifestation of ion specificity seen in aqueous systems in general. Our research is directed towards developing the theory and simulation tools to understand such phenomena in aqueous and biological systems.
I will first discuss our studies on elucidating the physical basis of K+-over-Na+ selectivity in the KcsA K+ channel. We find that the thermodynamics of the ion depends on those configurational states of the ion binding site in which the site is least distorted; Na+ is excluded because it distorts the site more than K+, the ion for which the channel evolved. On this basis, I will discuss the importance of the chemistry of ion-coordinating ligands and the protein outside the binding site (the bulk protein) in selectivity. I will indicate the importance of these issues for computational models describing ion binding as well.
While the KcsA system reveals the importance of the protein outside the site, we can also view the ion as stabilizing protein configurations. I will show how this perspective leads to a self-consistent molecular field description of the bulk protein in the context of a zinc finger protein, a system where protein folding and metal ion binding are intimately coupled.