The Physical Origin of Intrinsic Bends in Double Helical DNA

Physics – Biological Physics

Scientific paper

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17 two-column pages, 12 integrated eps plates, RevTeX/LaTeX

Scientific paper

The macroscopic curvature induced in the double helical B-DNA by regularly repeated adenine tracts (A-tracts) is a long known, but still unexplained phenomenon. This effect plays a key role in DNA studies because it is unique in the amount and the variety of the available experimental information and, therefore, is likely to serve as a gate to the unknown general mechanisms of recognition and regulation of genome sequences. We report the results of molecular dynamics simulations of a 25-mer B-DNA fragment with a sequence including three A-tract phased with the helical screw. It represents the first model system where properly directed static curvature emerges spontaneously in conditions excluding any initial bias except the base pair sequence. The effect has been reproduced in three independent MD trajectories of 10-20 ns with important qualitative details suggesting that the final bent state is a strong attractor of trajectories form a broad domain of the conformational space. The ensemble of curved conformations, however, reveals significant microscopic heterogeneity in contradiction to all existing theoretical models of bending. Analysis of these unexpected observations leads to a new, significantly different hypothesis of the possible mechanism of intrinsic bends in the double helical DNA.

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