title: Reaction path ensemble of the B-Z-DNA transition: a comprehensive atomistic study.
abstract: Since its discovery in 1979, left-handed Z-DNA has evolved from an in vitro curiosity to a challenging DNA structure with crucial roles in gene expression, regulation and recombination. A fundamental question that has puzzled researchers for decades is how the transition from B-DNA, the prevalent right-handed form of DNA, to Z-DNA is accomplished. Due to the complexity of the B-Z-DNA transition, experimental and computational studies have resulted in several different, apparently contradictory models. Here, we use molecular dynamics simulations coupled with state-of-the-art enhanced sampling techniques operating through non-conventional reaction coordinates, to investigate the B-Z-DNA transition at the atomic level. Our results show a complex free energy landscape, where several phenomena such as over-stretching, unpeeling, base pair extrusion and base pair flipping are observed resulting in interconversions between different DNA conformations such as B-DNA, Z-DNA and S-DNA. In particular, different minimum free energy paths allow for the coexistence of different mechanisms (such as zipper and stretch-collapse mechanisms) that previously had been proposed as independent, disconnected models. We find that the B-Z-DNA transition--in absence of other molecular partners--can encompass more than one mechanism of comparable free energy, and is therefore better described in terms of a reaction path ensemble.
authors.affiliation: Center for High Performance Simulations and Department of Physics, North Carolina State University, Raleigh, NC 27695-8202, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Moradi
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Babin
authors.forename: Christopher
authors.initials: C
authors.lastname: Roland
authors.forename: Celeste
authors.initials: C
authors.lastname: Sagui
mesh_terms: D020029:Base Pairing; D059371:DNA, B-Form / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation
chemical_list: D059371:DNA, B-Form; D043542:DNA, Z-Form