title: DNA denaturation bubbles: free-energy landscape and nucleation/closure rates.
abstract: The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of denaturation is required by specific DNA-binding proteins.
authors.affiliation: Université de Toulouse, UPS, Laboratoire de Physique Théorique (IRSAMC), F-31062 Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Sicard
authors.affiliation: Université de Toulouse, UPS, Laboratoire de Physique Théorique (IRSAMC), F-31062 Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Destainville
authors.affiliation: Université de Toulouse, UPS, Laboratoire de Physique Théorique (IRSAMC), F-31062 Toulouse, France.
authors.forename: Manoel
authors.initials: M
authors.lastname: Manghi
mesh_terms: D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013696:Temperature
chemical_list: D004247:DNA