Right-handed twisting is a fundamental structural feature of beta -pleated
sheets in globular proteins which is critical for their geometry and functi
on. The origin of this twisting is poorly understood and has represented a
challenge for theoretical chemistry for almost 30 years. Density functional
theory using the B3LYP exchange-correlation functional and the split-valen
ce 6-31G** basis set has been utilized to investigate the structure and con
formational transitions of single and double-stranded antiparallel beta -sh
eet models to determine the driving force for the right-handed twisting. Ri
ght-handed twisting is found to be an intrinsic property of a peptide main
chain because of the difference in rotational potentials around N(sp(2))-C-
alpha(sp(3)) and C(sp(2))-C-alpha(sp(3)) bonds. The difference arises from
a tendency of the single C-alpha(sp(3))-C(sp(2)) bonds to eclipse the lone
pair of atoms N(sp(2)), which results in decreasing absolute values of dihe
dral angles phi but not psi. This tendency is suppressed by hydrogen bondin
g between adjacent CO and NH groups within single beta -strands, and releas
ed only when these bonds are disrupted by the interstrand CO . . . HN hydro
gen bonding. The results obtained constitute the following paradigm of the
origin of alpha -sheet twist: although right-handed twisting of beta -sheet
s in globular proteins is an inherent property of the peptide backbone with
in single beta -strands, it is unleashed by the interstrand hydrogen bondin
g in multistranded beta -sheets. The observed pleating, right-handed twisti
ng, skewed mutual orientation of beta -strands, and intrinsic conformationa
l variability of double-stranded antiparallel beta -sheet motifs in globula
r proteins are explained from the first principles.