Theoretical Studies of the Possible Origin of Intrinsic Static Bends in Double Helical DNA

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 unknown general mechanisms of recognition and regulation of genome sequences. In this paper, conformations of a 25-mer A-tract repeat have been studied by molecular dynamics simulations. It is shown that properly directed static curvature emerges spontaneously in independent MD trajectories starting from straight canonical A- and B-DNA forms. Dynamics converge to the same bent state in conditions excluding any initial bias except the base pair sequence. The ensemble of curved conformations, however, appears microscopically heterogeneous, 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 sequence-directed bends in double helical DNA.