  Structural bioinformatics and van der Waals density functional theory are
combined to investigate the mechanochemical impact of a major class of
histone-DNA interactions, namely the formation of salt bridges between arginine
residues in histones and phosphate groups on the DNA backbone. Principal
component analysis reveals that the configurational fluctuations of the
sugar-phosphate backbone display sequence-specific variability, and clustering
of nucleosomal crystal structures identifies two major salt bridge
configurations: a monodentate form in which the arginine end-group guanidinium
only forms one hydrogen bond with the phosphate, and a bidentate form in which
it forms two. Density functional theory calculations highlight that the
combination of sequence, denticity and salt bridge positioning enable the
histones to tunably activate specific backbone deformations via mechanochemical
stress. The results suggest that selection for specific placements of van der
Waals contacts, with high-precision control of the spatial distribution of
intermolecular forces, may serve as an underlying evolutionary design principle
for the structure and function of nucleosomes, a conjecture that is
corroborated by previous experimental studies.
