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 uniqu e in the amount and the variety of the available experimental information a nd, therefore, is likely to serve as a gate to unknown general mechanisms o f recognition and regulation of genome sequences. In this paper, conformati ons of a 25-mer A-tract repeat have been studied by molecular dynamics simu lations. It is shown that properly directed static curvature emerges sponta neously in independent MD trajectories starting from straight canonical A- and B-DNA forms. Dynamics converge to the same bent state in conditions exc luding any initial bias except the base pair sequence. The ensemble of curv ed conformations, however, appears microscopically heterogeneous, in contra diction to all existing theoretical models of bending. Analysis of these un expected observations leads to a new, significantly different hypothesis of the possible mechanism of sequence-directed bends in double helical DNA.