Statistical mechanics of base stacking and pairing in DNA melting

We propose a statistical mechanics model for DNA melting in which base stacking and pairing are explicitly introduced as distinct degrees of freedom. Unlike previous approaches, this model describes thermal denaturation of DNA secondary structure in the whole experimentally accessible temperature range. Base pairing is described through a zipper model, base stacking through an Ising model. We present experimental data on the unstacking transition, obtained exploiting the observation that at moderately low pH this transition is moved down to experimentally accessible temperatures. These measurements confirm that the Ising model approach is indeed a good description of base stacking. On the other hand, comparison with the experiments points to the limitations of the simple zipper model description of base pairing.Comment: 13 pages with figure

Modelling Disorder: the Cases of Wetting and DNA Denaturation

We study the effect of the composition of the genetic sequence on the melting temperature of double stranded DNA, using some simple analytically solvable models proposed in the framework of the wetting problem. We review previous work on disordered versions of these models and solve them when there were not preexistent solutions. We check the solutions with Monte Carlo simulations and transfer matrix numerical calculations. We present numerical evidence that suggests that the logarithmic corrections to the critical temperature due to disorder, previously found in RSOS models, apply more generally to ASOS and continuous models. The agreement between the theoretical models and experimental data shows that, in this context, disorder should be the crucial ingredient of any model while other aspects may be kept very simple, an approach that can be useful for a wider class of problems. Our work has also implications for the existence of correlations in DNA sequences.Comment: Final published version. Title and discussion modified. 6 pages, 3 figure

Experimental and theoretical studies of sequence effects on the fluctuation and melting of short DNA molecules

Understanding the melting of short DNA sequences probes DNA at the scale of the genetic code and raises questions which are very different from those posed by very long sequences, which have been extensively studied. We investigate this problem by combining experiments and theory. A new experimental method allows us to make a mapping of the opening of the guanines along the sequence as a function of temperature. The results indicate that non-local effects may be important in DNA because an AT-rich region is able to influence the opening of a base pair which is about 10 base pairs away. An earlier mesoscopic model of DNA is modified to correctly describe the time scales associated to the opening of individual base pairs well below melting, and to properly take into account the sequence. Using this model to analyze some characteristic sequences for which detailed experimental data on the melting is available [Montrichok et al. 2003 Europhys. Lett. {\bf 62} 452], we show that we have to introduce non-local effects of AT-rich regions to get acceptable results. This brings a second indication that the influence of these highly fluctuating regions of DNA on their neighborhood can extend to some distance.Comment: To be published in J. Phys. Condensed Matte

Bubbles, clusters and denaturation in genomic DNA: modeling, parametrization, efficient computation

The paper uses mesoscopic, non-linear lattice dynamics based (Peyrard-Bishop-Dauxois, PBD) modeling to describe thermal properties of DNA below and near the denaturation temperature. Computationally efficient notation is introduced for the relevant statistical mechanics. Computed melting profiles of long and short heterogeneous sequences are presented, using a recently introduced reparametrization of the PBD model, and critically discussed. The statistics of extended open bubbles and bound clusters is formulated and results are presented for selected examples.Comment: to appear in a special issue of the Journal of Nonlinear Mathematical Physics (ed. G. Gaeta

Modelling DNA at the mesoscale: a challenge for nonlinear science?

Invited paper, in the series "Open Problems" of NonlinearityInternational audienceWhen it is viewed at the scale of a base pair, DNA appears as a nonlinear lattice. Modelling its properties is a fascinating goal. The detailed experiments that can be performed on this system impose constraints on the models and can be used as a guide to improve them. There are nevertheless many open problems, particularly to describe DNA at the scale of a few tens of base pairs, which is relevant for many biological phenomena

Trapping intermediates in the melting transition of DNA oligomers

We present a new method to study the melting transition of DNA oligonucleotides, which can quantify the presence of intermediate states. The approach is to combine UV spectroscopy with a method based on trapping intermediate states by quenching. The measurements yield both the average fraction of open base pairs (f) and the fraction of completely open molecules (p). If intermediate (partially open) states are not present, then p = f throughout the transition. In the presence of intermediate states, p < f. We demonstrate the method on the example of a 48mer sequence which is designed to open at one end and thus have intermediate states during melting. Then we show a different sequence design where the melting appears essentially as a two-states process. These experiments demonstrate the role played by end effects and sequence design in controlling the nature of the melting transition for DNA oligomers

Modelling disorder: the cases of wetting and DNA denaturation

We study the effect of the composition of the genetic sequence on the melting temperature of double stranded DNA, using some simple analytically solvable models proposed in the framework of the wetting problem. We review previous work on disordered versions of these models and solve them when there were not preexistent solutions. We check the solutions with Monte Carlo simulations and transfer matrix numerical calculations. We present numerical evidence that suggests that the logarithmic corrections to the critical temperature due to disorder, previously found in RSOS models, apply more generally to ASOS and continuous models. The agreement between the theoretical models and experimental data shows that, in this context, disorder should be the crucial ingredient of any model while other aspects may be kept very simple, an approach that can be useful for a wider class of problems. Our work has also implications for the existence of correlations in DNA sequences. Copyright EDP Sciences/Società Italiana di Fisica/Springer-Verlag 200787.15.-v Biomolecules: structure and physical properties, 68.35.Rh Phase transitions and critical phenomena, 05.40.-a Fluctuation phenomena, random processes, noise, and Brownian motion,