Reaction path ensemble of the B–Z-DNA transition: a comprehensive atomistic study

摘要: Since its discovery in 1979, left-handed Z-DNA has evolved from an vitro curiosity to a challenging DNA structure with crucial roles gene expression, regulation and recombination. A fundamental question that puzzled researchers for decades is how the transition B-DNA, prevalent right-handed form of DNA, accomplished. Due complexity B–Z-DNA transition, experimental computational studies have resulted several different, apparently contradictory models. Here, we use molecular dynamics simulations coupled state-of-the-art enhanced sampling techniques operating through non-conventional reaction coordinates, investigate at atomic level. Our results show complex free energy landscape, where phenomena such as over-stretching, unpeeling, base pair extrusion flipping are observed resulting interconversions between different conformations S-DNA. In particular, minimum paths allow coexistence mechanisms (such zipper stretch–collapse mechanisms) previously had been proposed independent, disconnected We find transition—in absence other partners—can encompass more than one mechanism comparable energy, therefore better described terms path ensemble.