Electrostatic Models for Calcium Binding Proteins

The binding of calcium ions to biomolecules has been investigated by comparing three continuum models, all presupposing the dominance of Coulombic interactions. To reflect disparity in polarization response of protein and solvent, the “refined” model (RM) incorporates an inhomogeneous static dielectric constant but admits only approximate analysis within the mean field ansatz. Conversely, the “primitive” model (PM), with a uniform dielectric response, yields to essentially exact solutions of the statistical mechanical problem by Monte Carlo simulation techniques. The “elementary” model (EM) further assumes linear thermal response and ignores steric constraints altogether to obtain a trivially evaluated, analytic result. Two contrasting biomolecules are considered:  the large, positively charged, extracellular serine protease subtilisin exhibiting a low affinity binding site and the smaller, negatively charged, intracellular, nonenzymatic protein buffer calbindin that binds calcium tenaciously. As function...