(451b) Stability Of Natively Unfolded Proteins As A Coil/globule Transition In Charge/hydropathy Space

Natively unfolded proteins display complex functions while lacking robust three-dimensional structures. Many empirical sequence based assays have been developed to predict the incidence of polypeptide disorder. One of the most physically appealing predictors is the charge/hydropathy correlation of Uversky, Gillespie, and Fink [Proteins Struct. Funct. Genet. (2000)], which establishes a stability boundary as a function of peptide charge and side chain hydrophobicity between compact and expanded protein conformations. Using extensive molecular simulations, we present results for a minimalist coarse-grained polypeptide model that displays a coil/globule transition with an increasing fraction of hydrophobic monomers and decreasing net charge analogous to the empirical charge/hydropathy correlation. Comparing results from simulations with and without explicit counterions for the charged polypeptide monomers, we find that the near sequence length dependence of the stability boundary results from counterion adsorption to the globular surface. This model can serve as base case for introducing additional functionalities to study the interplay between distinct predictors for protein disorder.