Multisite Ion Models That Improve Coordination and Free Energy Calculations in Molecular Dynamics Simulations

Current ion models in molecular mechanics are simple spheres, and their interactions are solely determined from the van der Waals radius of the sphere and the total charge. Here, we introduce a model where we distribute the total charge of the ion into n-dummy centers that are placed in the direction of the coordinating atoms. We have parametrized this model for two divalent cations, Ca2+ and Mg2+, and have tested the model’s accuracy in a variety of simulations. With this model we are not only able to correctly predict the free energies and selectivity for cation binding sites in proteins and nucleic acids, but we achieve better coordination geometries and can capture more subtle effects such as the exchange of inner shell waters. Additionally, this model does not employ higher-order electrostatics and thus can be easily used with standard force fields.