  Although recent spectroscopic studies of chemically denatured proteins hint
at significant nonrandom residual structure, the results of extensive small
angle X-ray scattering studies suggest random coil behavior, calling for a
coherent understanding of these seemingly contradicting observations. Here, we
report the results of a Monte Carlo study of the effects of two types of local
structures, a helix and Polyproline II (PPII) helix, on the dimensions of
random coil polyalanine chains viewed as a model of highly denatured proteins.
With an alpha helix content of 20%, corresponding to the Ramachandran
probability of being in the helical basin, experimentally observed radii of
gyration are recovered. Experimental radii are similarly recovered at an a
helix content of 87%, providing an explanation for the previously puzzling
experimental finding that the dimensions of the highly helical methanol-induced
unfolded state are experimentally indistinguishable from those of the
helix-poor urea-unfolded state. In contrast, the radius of gyration increases
monotonically with increasing PPII content, and is always more expanded than
the dimensions observed experimentally. These results suggest that PPII is
unlikely the sole, dominant preferred conformation for unfolded proteins.
