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SYIM: Intrinsic Modes

SYIM 1: Intrinsic Modes I

SYIM 1.2: Hauptvortrag

Donnerstag, 30. März 2006, 15:00–15:30, HSZ 04

Can we predict DNA biological activity from the study of its local fluctuations? — •Michel Peyrard¹, T.S. van Erp¹, S. Cuesta-Lopez², and J.-G. Hagmann¹ — ¹Laboratoire de Physique, Ecole Normale Supérieure de Lyon, 46 allée d’Italie, 69364 Lyon Cedex 07, France — ²University of Zaragoza, Dept. Física de la Materia Condensada, c/ Pedro Cerbuna s/n, 50009 Zaragoza, Spain

DNA dynamics is essential for its biological function. The genetic code could not be read without a local unwinding of the double helix, and large openings, the so-called “DNA bubbles”, are supposed to allow the formation of some specific DNA structures, such as the T-loop that stabilizes the end of the chromosomes.
Mesoscopic DNA models give a fairly accurate description of the thermal denaturation of DNA, i.e. the separation of the two strands by heating, and they predict the existence of localized fluctuations which are reminiscent of the “breathing” of the double helix observed by biologists.
Thus it is tempting to try to use these models to predict the biological activity of DNA. It has been speculated that the formation of bubbles of several base-pairs, due to thermal fluctuations, are indicators of biologically active sites. Comparison between molecular dynamics simulations of the PBD DNA model and experiments suggest that it could be the case, but this observation is however difficult because large bubbles appear only seldom so that the statistical significance of the results can be questioned. We introduce a new method, that is orders-of-magnitude faster than molecular dynamics to analyze these bubbles and show that presently the PDB model is not yet able to detect biologically active sites.
This does not imply that DNA fluctuations are not signs of the biological meaning of some sections of the genetic code, but could mean that the model is not yet able to properly relate the local opening and the base-pair sequence. In order to improve it, a comparison with experiments measuring the local fluctuations of DNA as a function of its sequence is necessary. We discuss such experiments and introduce some improvements of the model to bring it closer to the goal of predicting biological activity of DNA from physical studies of a highly simplified model.