Ionic force field optimization and modified ion-pair mixing rules

We propose an optimization scheme to obtain good ionic force fields for classical simulations of salt solutions, also of biological relevance. Our work is based on Molecular Dynamics simulations with explicit (SPC/E) water for different halide and alkali ions forming salt solutions at finite ion concentration. The force field derivation technique we propose is based on a simultaneous optimization of single-ion and ion-pair properties and the determination of the cation-anion interaction parameters (traditionally given by the mixing rules). From the finite-concentration simulations, thermodynamic properties of the salt solutions are derived, using the Kirkwood-Buff theory of solutions, and compared to relevant experimental data. For the rather size-symmetric salt solutions involving bromide and chloride ions, this scheme using the standard mixing rules works fine. For the iodide and fluoride solutions, corresponding to the largest and smallest anion we have considered, a rescaling of the mixing rules was necessary. In this respect, we have introduced scaling factors for the cation-anion Lennard-Jones interaction that quantify deviations from the standard mixing rules. We discuss the efficiency and complications of the proposed ionic force field optimization scheme.