Polarizable Force Field for DNA Based on the Classical Drude Oscillator: I. Refinement Using Quantum Mechanical Base Stacking and Conformational Energetics

Empirical force fields seek to relate the configuration of a set of atoms to its energy, thus yielding the forces governing its dynamics, using classical physics rather than more expensive quantum mechanical calculations that are computationally intractable for large systems. Most force fields used...

Full description

Saved in:
Bibliographic Details
Published in:Journal of chemical theory and computation 2017-05, Vol.13 (5), p.2053-2071
Main Authors: Lemkul, Justin A, MacKerell, Alexander D
Format: Article
Language:English
Subjects:
Computer simulation
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA, A-Form - chemistry
DNA, B-Form - chemistry
DNA, Z-Form - chemistry
Models, Chemical
Molecular chains
Molecular dynamics
Molecular Dynamics Simulation
Nucleic Acid Conformation
Parameterization
Potential energy
Quantum mechanics
Quantum Theory
Stacking
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Empirical force fields seek to relate the configuration of a set of atoms to its energy, thus yielding the forces governing its dynamics, using classical physics rather than more expensive quantum mechanical calculations that are computationally intractable for large systems. Most force fields used to simulate biomolecular systems use fixed atomic partial charges, neglecting the influence of electronic polarization, instead making use of a mean-field approximation that may not be transferable across environments. Recent hardware and software developments make polarizable simulations feasible, and to this end, polarizable force fields represent the next generation of molecular dynamics simulation technology. In this work, we describe the refinement of a polarizable force field for DNA based on the classical Drude oscillator model by targeting quantum mechanical interaction energies and conformational energy profiles of model compounds necessary to build a complete DNA force field. The parametrization strategy employed in the present work seeks to correct weak base stacking in A- and B-DNA and the unwinding of Z-DNA observed in the previous version of the force field, called Drude-2013. Refinement of base nonbonded terms and reparametrization of dihedral terms in the glycosidic linkage, deoxyribofuranose rings, and important backbone torsions resulted in improved agreement with quantum mechanical potential energy surfaces. Notably, we expand on previous efforts by explicitly including Z-DNA conformational energetics in the refinement.
ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.7b00067