The impact of sequence periodicity on DNA mechanics: investigating the origin of A-tract's curvature.

ABSTRACT

Periodic sequences in phase with DNA helical shape are prevalent in genomes due to their capacity to modulate DNA elasticity on a global scale. However, how this occurs is not well understood. We use all-atom molecular dynamics simulations on 40 bp DNA fragments to assess the effect of periodicity on bending, twisting, and stretch elasticity. We observe that DNA static curvature is the mechanical parameter most influenced by periodicity, with A-tract sequences having the greatest effect. A-tracts generate global curvature by bending in distinct directions (minor groove and backbones) that complement the bending of the rest of DNA, which predominantly is towards the major groove. Even if A-tracts are rigid at the local scale, these small bends integrate with the greater bends from the sequences between, producing an amplifying effect. As a result, our findings support a 'delocalized bend' model in which the A-tract operates as an 'adaptable mechanical part'. By understanding how global curvature emerges from local fluctuations, we reconcile previous contradictory theories and open an avenue for manipulating DNA mechanics through sequence design.