Balancing the interactions of ions, water, and DNA in the Drude polarizable force field.

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TitleBalancing the interactions of ions, water, and DNA in the Drude polarizable force field.
Publication TypeJournal Article
Year of Publication2014
AuthorsSavelyev, A, Mackerell, AD
JournalJ Phys Chem B
Volume118
Issue24
Pagination6742-57
Date Published2014 Jun 19
ISSN1520-5207
KeywordsDNA, Electrolytes, Gases, Ions, Molecular Dynamics Simulation, Osmotic Pressure, Quantum Theory, Thermodynamics, Water
Abstract

Recently we presented a first-generation all-atom Drude polarizable force field for DNA based on the classical Drude oscillator model, focusing on optimization of key dihedral angles followed by extensive validation of the force field parameters. Presently, we describe the procedure for balancing the electrostatic interactions between ions, water, and DNA as required for development of the Drude force field for DNA. The proper balance of these interactions is shown to impact DNA stability and subtler conformational properties, including the conformational equilibrium between the BI and BII states, and the A and B forms of DNA. The parametrization efforts were simultaneously guided by gas-phase quantum mechanics (QM) data on small model compounds and condensed-phase experimental data on the hydration and osmotic properties of biologically relevant ions and their solutions, as well as theoretical predictions for ionic distribution around DNA oligomer. In addition, fine-tuning of the internal base parameters was performed to obtain the final DNA model. Notably, the Drude model is shown to more accurately reproduce counterion condensation theory predictions of DNA charge neutralization by the condensed ions as compared to the CHARMM36 additive DNA force field, indicating an improved physical description of the forces dictating the ionic solvation of DNA due to the explicit treatment of electronic polarizability. In combination with the polarizable DNA force field, the availability of Drude polarizable parameters for proteins, lipids, and carbohydrates will allow for simulation studies of heterogeneous biological systems.

DOI10.1021/jp503469s
Alternate JournalJ Phys Chem B
PubMed ID24874104
PubMed Central IDPMC4064693
Grant ListR01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States