Polarizable Force Field for DNA Based on the Classical Drude Oscillator: II. Microsecond Molecular Dynamics Simulations of Duplex DNA

The structure and dynamics of DNA are governed by a sensitive balance between base stacking and pairing, hydration, and interactions with ions. Force-field models that include explicit representations of electronic polarization are capable of more accurately modeling the subtle details of these interactions versus commonly used additive force fields. In this work, we validate our recently refined polarizable force field for DNA based on the classical Drude oscillator model, in which electronic degrees of freedom are represented as negatively charged particles attached to their parent atoms via harmonic springs. The previous version of the force field, called Drude-2013, produced stable A- and B-DNA trajectories on the order of hundreds of nanoseconds, but deficiencies were identified that included weak base stacking ultimately leading to distortion of B-DNA duplexes and unstable Z-DNA. As a result of extensive refinement of base nonbonded terms and bonded parameters in the deoxyribofuranose sugar and phosphodiester backbone, we demonstrate that the new version of the Drude DNA force field is capable of simulating A- and B-forms of DNA on the microsecond time scale and the resulting conformational ensembles agree well with a broad set of experimental properties, including solution X-ray scattering profiles. In addition, simulations of Z-form duplex DNA in its crystal environment are stable on the order of 100 ns. The revised force field is to be called Drude-2017.