Molecular dynamics simulations of aqueous ion solutions

Abstract

The activity and function of many macromolecules in cellular environments are coupled with the binding of ions such as alkaline earth metal ions and poly oxo anions. These ions are involved in the regulation of important processes such as protein crystallization, nucleic acid and protein stability, enzyme activity, and many others. The exact mechanism of ion specificity is still elusive. In principle, computer simulations can be used to help provide a molecular level understanding of the dynamics of hydrated ions and their interactions with the biomolecules. However, most of the force fields available today often fail to accurately reproduce the properties of ions in aqueous environments. Here we develop a classical non polarizable force field for aqueous alkaline earth metal halides (MX₂) where M = Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺ and X = Cl⁻, Br⁻, I⁻, and for some biologically important oxo anions which are NO₃⁻, ClO₄⁻, H₂PO₄⁻ and SO₄²⁻, for use in biomolecular simulations. The new force field parameters are developed to reproduce the experimental Kirkwood-Buff integrals. The Kirkwood-Buff integrals can be used to quantify the affinity between molecular species in solution. This helps to capture the fine balance between the interactions of ions and water. Since this new force field can reproduce the experimental Kirkwood-Buff integrals for most concentrations of the respective salts, they are capable of reproduce the experimental activity derivatives, partial molar volumes, and excess coordination numbers. Use of these new models in MD simulations also leads to reasonable diffusion constants and dielectric decrements. Attempts to develop force field parameters for CO₃²⁻, HPO₄²⁻ and PO₄³⁻ ions were unsuccessful due to an excessive aggregation behavior in the simulations. Therefore, in an effort to overcome this aggregation behavior in the simulations, we have investigated scaling the anion to water interaction strength, and also the possibility of using a high frequency permittivity in the simulations. The strategy of increasing relative permittivity of the system to mimic electronic screening effects are particularly promising for decreasing the excessive ion clustering observed in the MD simulations.