Is the Solution Activity Derivative Sufficient to Parametrize Ion-Ion Interactions? Ions for TIP5P Water

Biomolecular processes involve hydrated ions, and thus molecular simulations of such processes require accurate force-field parameters for these ions. In the best force-fields, both ion-water and anion-cation interactions are explicitly parametrized. First, the ion Lennard-Jones parameters are optimized to reproduce, for example, single ion solvation free energies; then ion-pair interactions are adjusted to match experimental activity or activity derivatives. Here, we apply this approach to derive optimized parameters for concentrated NaCl, KCl, MgCl₂, and CaCl₂ salt solutions, to be used with the TIP5P water model. These parameters are of interest because of a number of desirable properties of the TIP5P water model, especially for the simulation of carbohydrates. The results show, that this state of the art approach is insufficient, because the activity derivative often reaches a plateau near the target experimental value, for a wide range of parameter values. The plateau emerges from the interconversion between different types of ion pairs, so parameters leading to equally good agreement with the target solution activity or activity derivative yield very different solution structures. To resolve this indetermination, a second target property, such as the experimentally determined ion-ion coordination number, is required to uniquely determine anion-cation interactions. Simulations show that combining activity derivatives and coordination number as experimental target properties to parametrize ion-ion interactions, is a powerful method for reliable ion-water force field parametrization, and gives insight into the concentration of contact or solvent shared ion pairs in a wide range of salt concentrations. For the alkali and halide ions Li⁺, Rb⁺, Cs⁺, F^-, Br^-, and I^-, we present ion-water parameters appropriate at infinite dilution only.