title: 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.
abstract: 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+.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland , Baltimore, MD 21201, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Lemkul
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland , Baltimore, MD 21201, United States.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
mesh_terms: D008274:Magnesium / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry*; D012996:Solutions; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D014867:Water; D012313:RNA; D008274:Magnesium