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Mardi 21 octobre 2014-14:00

DNA denaturation bubble : Free-Energy landscape and nucleation/closure rates

Francois Sicard (LPT Toulouse, IRSAMC, UPS-CNRS)

par Gabriel LeMarié - 21 octobre 2014

Although the DNA structure in double-helix is robust enough to enable the preservation of the genetic code, it is sufficiently loose to allow the formation of denaturation bubbles, i.e. the cooperative opening of a sequence of consecutive base-pairs, even at physiological temperature. DNA opening is central in biological mechanisms such as replication, transcription, repair, or protein binding.

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 (resp. closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated to the crossing of a free-energy barrier of 22 k_B T (resp. 13 k_B T) 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 the 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, these more than 4 base-pair bubbles are of biological relevance, for example when a preexisting state of denaturation is required by specific DNA-binding proteins.

Post-scriptum :

contact : G. Lemarié