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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Moradi M,Babin V,Roland C,Sagui Cdoi
10.1093/nar/gks1003subject
Has Abstractpub_date
2013-01-07 00:00:00pages
33-43issue
1eissn
0305-1048issn
1362-4962pii
gks1003journal_volume
41pub_type
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