title: Determination of Electrostatic Parameters for a Polarizable Force Field Based on the Classical Drude Oscillator.
abstract: A procedure to determine the electrostatic parameters has been developed for a polarizable empirical force field based on the classical Drude oscillator model. Atomic charges and polarizabilities for a given molecule of interest were derived from restrained fitting to quantum-mechanical electrostatic potentials (ESP) calculated at the B3LYP/ cc-pVDZ or B3LYP/aug-cc-pVDZ levels on grid points located on concentric Connolly surfaces. The determination of the atomic polarizabilities requires a series of perturbed ESP maps, each one representing the electronic response of the molecule in the presence of a background charge placed on Connolly surfaces primarily along chemical bonds and lone pairs. Reference values for the partial atomic charges were taken from the CHARMM27 additive all-atom force field, and those for the polarizabilities were based on adjusted Miller's ahp atomic polarizability values. The fitted values of atomic polarizabilities were scaled to reflect the reduced polarization expected for the condensed media and/or to correct for the systematic underestimation of experimental molecular polarizabilities by B3LYP calculations. Following correction of the polarizabilities, the atomic charges were adjusted to reproduce gas-phase dipole moments. The developed scheme has been tested on a set of small molecules representing functional moieties of nucleic acids. The derived electrostatic parameters have been successfully applied in a preliminary polarizable molecular dynamics simulation of a DNA octamer in a box of water with sodium counterions. Thus, this study confirms the feasibility of the use of a polarizable force field based on a classical Drude model for simulations of biomolecules in the condensed phase.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Anisimov
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamoureux
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Vorobyov
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Niu
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, Département de physique, Université de Montréal, C.P. 6128, succ. centre-ville, Montréal, Québec, Canada H3C 3J7, and Department of Biochemistry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell