Breathing dynamics in heteropolymer DNA

The denaturation of double-stranded DNA as function of force and temperature is discussed. At room temperature, sequence heterogeneity dominates the physics of single molecule force-extension curves starting about 7 piconewtons of below a ~15 pN unzipping transition. The dynamics of the unzipping fork exhibits anomalous drift and diffusion in a similar range above this transition. Energy barriers near the transition scale as the square root of the genome size. Recent observat...

We propose a new statistical mechanics model for the melting transition of DNA. Base pairing and stacking are treated as separate degrees of freedom, and the interplay between pairing and stacking is described by a set of local rules which mimic the geometrical constraints in the real molecule. This microscopic mechanism intrinsically accounts for the cooperativity related to the free energy penalty of bubble nucleation. The model describes both the unpairing and unstacking p...

Statistical DNA models available in the literature are often effective models where the base-pair state only (unbroken or broken) is considered. Because of a decrease by a factor of 30 of the effective bending rigidity of a sequence of broken bonds, or bubble, compared to the double stranded state, the inclusion of the molecular conformational degrees of freedom in a more general mesoscopic model is needed. In this paper we do so by presenting a 1D Ising model, which describe...

It has been speculated that bubble formation of several base-pairs due to thermal fluctuations is indicatory for biological active sites. Recent evidence, based on experiments and molecular dynamics (MD) simulations using the Peyrard-Bishop-Dauxois model, seems to point in this direction. However, sufficiently large bubbles appear only seldom which makes an accurate calculation difficult even for minimal models. In this letter, we introduce a new method that is orders of magn...

From a nanoscience perspective, cellular processes and their reduced in vitro imitations provide extraordinary examples for highly robust few or single molecule reaction pathways. A prime example are biochemical reactions involving DNA molecules, and the coupling of these reactions to the physical conformations of DNA. In this review, we summarise recent results on the following phenomena: We investigate the biophysical properties of DNA-looping and the equilibrium configurat...

We studied how the inhomogeneity of a sequence affects the phase transition that takes place at DNA melting. Unlike previous works, which considered thermodynamic quantities averaged over many different inhomogeneous sequences, we focused on precise sequences and investigated the succession of local openings that lead to their dissociation. For this purpose, we performed Transfer Integral type calculations with two different dynamical models, namely the heterogeneous Dauxois-...

The thermodynamical properties of heterogeneous DNA sequences are computed by path integral techniques applied to a nonlinear model Hamiltonian. The base pairs relative displacements are interpreted as time dependent paths whose amplitudes are consistent with the model potential for the hydrogen bonds between complementary strands. The portion of configuration space contributing to the partition function is determined, at any temperature, by selecting the ensemble of paths wh...

We study DNA denaturation by integrating elasticity -- as described by the Gaussian network model -- with bond binding energies, distinguishing between different base-pair and stacking energies. We use exact calculation, within the model, of the Helmholtz free-energy of any partial denaturation state, which implies that the entropy of all formed bubbles ("loops") is accounted for. Considering base-pair bond removal single events, the bond designated for opening is chosen by m...

We study the dynamics of denaturation bubbles in double-stranded DNA on the basis of the Poland-Scheraga model. We demonstrate that the associated Fokker-Planck equation is equivalent to a Coulomb problem. Below the melting temperature the bubble lifetime is associated with the continuum of scattering states of the repulsive Coulomb potential, at the melting temperature the Coulomb potential vanishes and the underlying first exit dynamics exhibits a long time power law tail, ...

Based on modern single molecule techniques, we devise a number of possible experimental setups to probe local properties of DNA such as the presence of DNA-knots, loops or folds, or to obtain information on the DNA-sequence. Similarly, DNA may be used as a local sensor. Employing single molecule fluorescence methods, we propose to make use of the physics of DNA denaturation nanoregions to find out about the solvent conditions such as ionic strength, presence of binding protei...