Parameterization of Ca⁺²-Protein Interactions for Molecular Dynamics Simulations

Molecular dynamics simulations of Ca⁺² ions near protein were performed with three force fields: GROMOS96, OPLS-AA, and CHARMM22. The simulations reveal major, force-field dependent, inconsistencies in the interaction between the Ca⁺² ions with the protein. The variations are attributed to the nonbonded parameterizations of the Ca⁺²- carboxylates interactions. The simulations results were compared to experimental data, using the Ca⁺²-HCOO^- equilibrium as a model. The OPLS-AA force field grossly overestimates the binding affinity of the Ca ⁺² ions to the carboxylate whereas the GROMOS96 and CHARMM22 force fields underestimate the stability of the complex. Optimization of the Lennard-Jones parameters for the Ca⁺²-carboxylate interactions were carried out, yielding new parameters which reproduce experimental data.