Dataset Information

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+.

SUBMITTER: Lemkul JA

PROVIDER: S-EPMC5148688 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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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.

Lemkul Justin A JA MacKerell Alexander D AD

The journal of physical chemistry. B 20161027 44

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 ...[more]

PMID: 27759379

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Project description:A polarizable force field for nucleic acid bases based on the classical Drude oscillator model is presented. Parameter optimization was performed to reproduce crystallographic geometries, crystal unit cell parameters, heats of sublimation, vibrational frequencies and assignments, dipole moments, molecular polarizabilities and quantum mechanical base-base and base-water interaction energies. The training and validation data included crystals of unsubstituted and alkyl-substituted adenine, guanine, cytosine, uracil, and thymine bases, hydrated crystals, and hydrogen bonded base pairs. Across all compounds, the RMSD in the calculated heats of sublimation is 4.1%. This equates to an improvement of more than 2.5 kcal/mol in accuracy compared to the nonpolarizable CHARMM27 force field. However, the level of agreement with experimental molecular volume decreased from 1.7% to 2.1% upon moving from the nonpolarizable to the polarizable model. The representation of dipole moments is significantly improved with the Drude polarizable force field. Unlike in additive force fields, there is no requirement for the gas-phase dipole moments to be overestimated, illustrating the ability of the Drude polarizable force field to treat accurately differently dielectric environments and indicating the improvements in the electrostatic model. Validation of the model was performed on the basis of the calculation of the gas-phase binding enthalpies of base pairs obtained via potential of mean force calculations; the additive and polarizable models both performed satisfactorily with average differences of 0.2 and 0.9 kcal/mol, respectively, and rms differences of 1.3 and 1.7 kcal/mol, respectively. Overall, considering the number of significant improvements versus the additive CHARMM force field, the incorporation of explicit polarizability into the force field for nucleic acid bases represents an additional step toward accurate computational modeling of biological systems.

Dataset Information

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.

Publications

Balancing the Interactions of Mg<sup>2+</sup> in Aqueous Solution and with Nucleic Acid Moieties For a Polarizable Force Field Based on the Classical Drude Oscillator Model.

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