FIGURE 6.

Model for metal ion binding to protein Ca(II) sites. (A) A simplified schematic view of metal ion binding to a partially unfolded, empty Ca(II) site. The binding event occurs when the binding site folds around the metal ion, releasing water of hydration from the metal ion and from ligand residues. (B) A schematic diagram of the relationship between the binding free energy and ionic radius. The total binding free energy (ΔG_B) is the bold curve, shown with its three additive components: the free energy of ligand dehydration and deprotonation (ΔG_dp) is predicted to be independent of metal ion radius; the free energy of metal ion dehydration (ΔG_dm) is predicted to increase inversely as the ionic radius decreases (Rashin & Honig, 1985); the free energy of association of the dehydrated ion and the site (Δ _m·p) is predicted to exhibit a minimum at the optimal ionic radius, while increasing both for larger radii which cause crowding in the site and for smaller radii which have reduced metal-ligand electrostatic stabilization.