Molecular Dynamics Simulations of Nucleic Acids with a Generalized Born Solvation Model

Abstract

A generalized Born (GB) model has been applied to molecular dynamics simulations of the A- and B-forms of a duplex DNA d(CCAACGTTGG)2 and the corresponding duplex RNA r(CCAACGUUGG)2, resulting in good agreement with simulations using explicit water solvent in terms of both structure and energetics. In particular, the A → B energy differences derived from GB trajectories for both DNA and RNA closely match those obtained earlier using explicit water simulations and finite-difference Poisson−Boltzmann calculations. A GB simulation starting from A-form DNA converges to B-DNA within 20 ps, more than 20 times faster than the transition from A- to B-DNA in explicit solvent simulations. For B-form d(CCAACGTTGG)2, fluctuations about the mean are highly correlated between GB and explicit water simulations, being slightly larger in the former, and the essential subspaces found from principal component analysis overlap to a high degree. Hence, for many purposes this parametrization offers an alternative to more expensive explicit water simulations for studies of nucleic acid energetics and structure.