The observed sequence dependence of the mean twist angles in 38 B-DNA
crystal structures can be understood in terms of simple geometrical fe
atures of the constituent base-pairs. Structures with low twist appear
to unwind in response to severe steric clashes of large exocyclic gro
ups (such as NH2-NH2) in the major and minor grooves, while those with
high twist are subjected to lesser contacts (H-O and H-H). We offer a
simple clash function that depends on base-pair morphology (i.e. the
chemical constitution of base-pairs) and satisfactorily accounts for t
he twist angles of the ten common Watson-Crick dimer steps both in the
solid state and in solution. The twist-clash correlation that we find
here still holds when extended to modified bases. In addition to Call
adine's purine-purine clashes, we add other close contacts between bas
es in the grooves, and consider the conformational restrictions on the
geometry of the sugar-phosphate backbone (namely, we emphasize the te
ndency of DNA to conserve virtual backbone length). The significance o
f this finding is threefold: (1) sequence-dependent DNA twisting is di
rectly involved in protein-DNA interactions; (2) strong correlation be
tween Twist and Roll helps to elucidate the bending of the double heli
x as a function of base sequence; (3) it is possible to anticipate the
effects of chemical modifications on twisting and bending. The mutual
correlations of other structural parameters with the twist make this
angle a primary determinant of DNA conformational heterogeneity.