Sommaire:

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.

Pour plus d'informations, merci de contacter Palmeri J.