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. According to it, the intrinsic bends in B-DNA may represent one of the consequences of the compressed frustrated state of its backbone. The compressed backbone hypothesis agrees with many data and explains some controversial experimental observations. The original arguments of this theory came out from MD simulations of a DNA fragment with a strong bending propensity. Its sequence, however, was not experimental. It was constructed empirically so as to maximize the magnitude of bending in calculations. To make sure that our computations reproduce the experimental effect we carried out similar simulations with an A-tract repeat of a natural base pair sequence found in a bent locus of a minicircle DNA. We demonstrate spontaneous development of static curvature in the course of MD simulations excluding any initial bias except the base pair sequence. Its direction and magnitude agree with experimental estimates. The results confirm earlier qualitative conclusions and agree with the hypothesis of a compressed backbone as the origin of static bending in B-DNA.