All-atom polarizable force field for DNA based on the classical Drude oscillator model.

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TitleAll-atom polarizable force field for DNA based on the classical Drude oscillator model.
Publication TypeJournal Article
Year of Publication2014
AuthorsSavelyev, A, Mackerell, AD
JournalJ Comput Chem
Volume35
Issue16
Pagination1219-39
Date Published2014 Jun 15
ISSN1096-987X
KeywordsComputer Simulation, DNA, Hydrogen Bonding, Models, Chemical, Models, Molecular, Nucleic Acid Conformation, Software
Abstract

Presented is a first generation atomistic force field (FF) for DNA in which electronic polarization is modeled based on the classical Drude oscillator formalism. The DNA model is based on parameters for small molecules representative of nucleic acids, including alkanes, ethers, dimethylphosphate, and the nucleic acid bases and empirical adjustment of key dihedral parameters associated with the phosphodiester backbone, glycosidic linkages, and sugar moiety of DNA. Our optimization strategy is based on achieving a compromise between satisfying the properties of the underlying model compounds in the gas phase targeting quantum mechanical (QM) data and reproducing a number of experimental properties of DNA duplexes in the condensed phase. The resulting Drude FF yields stable DNA duplexes on the 100-ns time scale and satisfactorily reproduce (1) the equilibrium between A and B forms of DNA and (2) transitions between the BI and BII substates of B form DNA. Consistency with the gas phase QM data for the model compounds is significantly better for the Drude model as compared to the CHARMM36 additive FF, which is suggested to be due to the improved response of the model to changes in the environment associated with the explicit inclusion of polarizability. Analysis of dipole moments associated with the nucleic acid bases shows the Drude model to have significantly larger values than those present in CHARMM36, with the dipoles of individual bases undergoing significant variations during the MD simulations. Additionally, the dipole moment of water was observed to be perturbed in the grooves of DNA.

DOI10.1002/jcc.23611
Alternate JournalJ Comput Chem
PubMed ID24752978
PubMed Central IDPMC4075971
Grant ListR01 GM070855 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States