Bubble statistics and positioning in superhelically stressed DNA

We present a general framework to study the thermodynamic denaturation of double-stranded DNA under superhelical stress. We report calculations of position- and size-dependent opening probabilities for bubbles along the sequence. Our results are obtained from transfer-matrix solutions of the Zimm-Bragg model for unconstrained DNA and of a self-consistent linearization of the Benham model for superhelical DNA. The numerical efficiency of our method allows for the analysis of entire genomes and of random sequences of corresponding length ($10^6-10^9$ base pairs). We show that, at physiological conditions, opening in superhelical DNA is strongly cooperative with average bubble sizes of $10^2-10^3$ base pairs (bp), and orders of magnitude higher than in unconstrained DNA. In heterogeneous sequences, the average degree of base-pair opening is self-averaging, while bubble localization and statistics are dominated by sequence disorder. Compared to random sequences with identical GC-content, genomic DNA has a significantly increased probability to open large bubbles under superhelical stress. These bubbles are frequently located directly upstream of transcription start sites.Comment: to be appeared in Physical Review

Sequence sensitivity of breathing dynamics in heteropolymer DNA

We study the fluctuation dynamics of localized denaturation bubbles in heteropolymer DNA with a master equation and complementary stochastic simulation based on novel DNA stability data. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a biological sequence of the T7 bacteriophage. Quantitative agreement with data from fluorescence correlation spectroscopy (FCS) is demonstrated.Comment: 4 pages, 5 figures, to appear in Physical Review Letter

Breathing dynamics in heteropolymer DNA

While the statistical mechanical description of DNA has a long tradition, renewed interest in DNA melting from a physics perspective is nourished by measurements of the fluctuation dynamics of local denaturation bubbles by single molecule spectroscopy. The dynamical opening of DNA bubbles (DNA breathing) is supposedly crucial for biological functioning during, for instance, transcription initiation and DNA's interaction with selectively single-stranded DNA binding proteins. Motivated by this, we consider the bubble breathing dynamics in a heteropolymer DNA based on a (2+1)-variable master equation and complementary stochastic Gillespie simulations, providing the bubble size and the position of the bubble along the sequence as a function of time. We utilize new experimental data that independently obtain stacking and hydrogen bonding contributions to DNA stability. We calculate the spectrum of relaxation times and the experimentally measurable autocorrelation function of a fluorophore-quencher tagged base-pair, and demonstrate good agreement with fluorescence correlation experiments. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a promoter sequence of the T7 phage. The strong dependence on sequence, temperature and salt concentration for the breathing dynamics of DNA found here points at a good potential for nanosensing applications by utilizing short fluorophore-quencher dressed DNA constructs.Comment: 11 pages, 8 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

Total syntheses of conformationally-locked difluorinated pentopyranose analogues and a pentopyranosyl phosphate mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate

Inferring DNA sequences from mechanical unzipping data: the large-bandwidth case

The complementary strands of DNA molecules can be separated when stretched apart by a force; the unzipping signal is correlated to the base content of the sequence but is affected by thermal and instrumental noise. We consider here the ideal case where opening events are known to a very good time resolution (very large bandwidth), and study how the sequence can be reconstructed from the unzipping data. Our approach relies on the use of statistical Bayesian inference and of Viterbi decoding algorithm. Performances are studied numerically on Monte Carlo generated data, and analytically. We show how multiple unzippings of the same molecule may be exploited to improve the quality of the prediction, and calculate analytically the number of required unzippings as a function of the bandwidth, the sequence content, the elasticity parameters of the unzipped strands

Field induced quantum-Hall ferromagnetism in suspended bilayer graphene

We have measured the magneto-resistance of freely suspended high-mobility bilayer graphene. For magnetic fields $B>1$ T we observe the opening of a field induced gap at the charge neutrality point characterized by a diverging resistance. For higher fields the eight-fold degenerated lowest Landau level lifts completely. Both the sequence of this symmetry breaking and the strong transition of the gap-size point to a ferromagnetic nature of the insulating phase developing at the charge neutrality point.Comment: 7 pages, 5 figure