Hydrodynamic Radii of Intrinsically Disordered Proteins Determined from Experimental Polyproline II Propensities

The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PP (II)) structure. While intrinsic PP (II) propensities have been measured for the common biological amino acids in short peptides, the ability of these experimentally determined propensities to quantitatively reproduce structural behavior in intrinsically disordered proteins (IDPs) has not been established. Presented here are results from molecular simulations of disordered proteins showing that the hydrodynamic radius (R (h)) can be predicted from experimental PP (II) propensities with good agreement, even when charge-based considerations are omitted. The simulations demonstrate that R (h) and chain propensity for PP (II) structure are linked via a simple power-law scaling relationship, which was tested using the experimental R (h) of 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. Charge effects on R (h) were found to be generally weak when compared to PP (II) effects on R (h). Results from this study indicate that the hydrodynamic dimensions of IDPs are evidence of considerable sequence-dependent backbone propensities for PP (II) structure that qualitatively, if not quantitatively, match conformational propensities measured in peptides.