Balancing the Interactions of Mg2+ in Aqueous Solution and with Nucleic Acid Moieties For a Polarizable Force Field Based on the Classical Drude Oscillator Model.
Mg2+ ions are important in biological systems, particularly in stabilizing compact RNA folds. Mg2+ is strongly polarizing, and representing its interactions in heterogeneous environments is a challenge for empirical force field development. To date, the most commonly used force fields in molecular dynamics simulations utilize a pairwise additive approximation for electrostatic interactions, which cannot account for the significant polarization response in systems containing Mg2+ In the present work, we refine the interactions of Mg2+ with water, Cl ions, and nucleic acid moieties using a polarizable force field based on the classical Drude oscillator model. By targeting gas phase quantum mechanical interaction energies and geometries of hydrated complexes, as well as condensed phase osmotic pressure calculations, we present a model for Mg2+ that yields quantitative agreement with experimental measurements of water dissociation free energy and osmotic pressure across a broad range of concentrations. Notable is the direct modeling of steric repulsion between the water Drude oscillators and Mg2+ to treat the Pauli exclusion effects associated with overlap of the electron clouds of water molecules in the first hydration shell around Mg2+ Combined with the refined interactions with nucleic acid moieties, the present model represents a significant advancement in simulating nucleic acid systems containing Mg2+
The journal of physical chemistry. B