  Van der Waals density functional theory is integrated with analysis of a
non-redundant set of protein-DNA crystal structures from the Nucleic Acid
Database to study the stacking energetics of CG:CG base-pair steps,
specifically the role of cytosine 5-methylation. Principal component analysis
of the steps reveals the dominant collective motions to correspond to a tensile
'opening' mode and two shear 'sliding' and 'tearing' modes in the orthogonal
plane. The stacking interactions of the methyl groups globally inhibit CG:CG
step overtwisting while simultaneously softening the modes locally via
potential energy modulations that create metastable states. Additionally, the
indirect effects of the methyl groups on possible base-pair steps neighboring
CG:CG are observed to be of comparable importance to their direct effects on
CG:CG. The results have implications for the epigenetic control of DNA
mechanics.
