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

Abstract

The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PPII) structure. While intrinsic PPIIpropensities 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 (Rh) can be predicted from experimental PPIIpropensities with good agreement, even when charge-based considerations are omitted. The simulations demonstrate that Rhand chain propensity for PPIIstructure are linked via a simple power-law scaling relationship, which was tested using the experimental Rhof 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. Charge effects on Rhwere found to be generally weak when compared to PPIIeffects on Rh. Results from this study indicate that the hydrodynamic dimensions of IDPs are evidence of considerable sequence-dependent backbone propensities for PPIIstructure that qualitatively, if not quantitatively, match conformational propensities measured in peptides.