Molecular Dynamics Investigations of Z[WC] DNA and the B to Z-DNA Transition

Abstract

Although DNA is most commonly found in the right-handed B-DNA structure, it is known that biologically active systems also contain left-handed ZII-DNA. We investigate the possibility that Z[WC]-DNA serves as an intermediate structure in the B to ZII transition. Molecular dynamics simulations indicate that Z[WC] forms stable structures with the current AMBER nucleic acid force field. Steered molecular dynamics simulations indicate that, for collective transitions of the whole strand, the B-Z[WC]-ZII pathway may have a lower free-energy barrier than the direct B-ZII pathway. A careful combination of steered and targeted molecular dynamics, along with umbrella sampling, are used to produce potentials of mean force for both the direct and the B-Z[WC]-ZII pathways.