Molecular Origins of DNA Flexibility: Sequence Effects on Conformational and Mechanical Properties

A central question in biophysics is whether DNA sequence affects its mechanical properties, which are thought to influence nucleosome positioning and gene expression. Previous attempts to answer this question have been hindered by an inability to resolve DNA structure and dynamics at the base-pair level. Here we use a model to measure the effects of sequence on the stability of DNA under bending. Sequence is shown to influence DNA's flexibility and its ability to form kinks, which arise when certain motifs slide past others to form non-native contacts. A mechanism for nucleosome positioning is proposed in which sequence influences DNA-histone binding by altering the local base-pair-level structure when subject to the curvature necessary for binding.