Molecular Dynamics Studies of Sequence-directed Curvature in Bending Locus of Trypanosome Kinetoplast DNA

The macroscopic curvature induced in the double helical B-DNA by regularly repeated adenine tracts (A-tracts) plays an exceptional role in structural studies of DNA because this effect presents the most well-documented example of sequence specific conformational modulations. Recently, a new hypothesis of its physical origin has been put forward, based upon the results of molecular dynamics simulations of a 25-mer fragment with three A-tracts phased with the helical screw. Its sequence, however, had never been encountered in experimental studies, but was constructed empirically so as to maximize the magnitude of bending in specific computational conditions. Here we report the results of a similar investigation of another 25-mer B-DNA fragment now with a natural base pair sequence found in a bent locus of a minicircle DNA. It is shown that the static curvature of a considerable magnitude and stable direction towards the minor grooves of A-tracts emerges spontaneously in conditions excluding any initial bias except the base pair sequence. Comparison of the bending dynamics of these two DNA fragments reveals both qualitative similarities and interesting differences. The results suggest that the A-tract induced bending obtained in simulations reproduces the natural phenomenon and validates the earlier conclusions concerning its possible mechanism.