Classical Drude Polarizable Force Field Model for Methyl Phosphate and Its Interactions with Mg.

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TitleClassical Drude Polarizable Force Field Model for Methyl Phosphate and Its Interactions with Mg.
Publication TypeJournal Article
Year of Publication2018
AuthorsVilla, F, Mackerell, AD, Roux, B, Simonson, T
JournalJ Phys Chem A
Volume122
Issue29
Pagination6147-6155
Date Published2018 Jul 26
ISSN1520-5215
Abstract

Phosphate groups are essential components of nucleic acids and proteins, whose interactions with solvent, metal ions, and ionic side chains help control folding and binding. Methyl phosphate (MP) represents a simple analog of phosphate moieties that are post-translation modifications in proteins and present at the termini of nucleic acids, among other environments. In the present study, we optimized parameters for use in polarizable molecular dynamics simulations of MP in its mono- and dianionic forms, MP ≡ CHHPO and MP ≡ CHPO, along with P ≡ HPO, in the context of the classical Drude oscillator model. Parameter optimization was done in a manner consistent with the remainder of the Drude molecular mechanics force field, choosing atomic charges and polarizabilities to reproduce molecular properties from quantum mechanics as well as experimental hydration free energies. Optimized parameters were similar to existing dimethyl phosphate parameters, with a few significant differences. The developed parameters were then used to compute magnesium binding affinities in aqueous solution, using alchemical molecular dynamics free energy simulations. Good agreement with experiment was obtained, and outer sphere binding was shown to be predominant for MP and MP.

DOI10.1021/acs.jpca.8b04418
Alternate JournalJ Phys Chem A
PubMed ID29966419
PubMed Central IDPMC6062457
Grant ListR01 GM051501 / GM / NIGMS NIH HHS / United States
R01 GM072558 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States