MODELING PROTEIN STABILITY AS HETEROPOLYMER COLLAPSE

This chapter reviews a simple model for the stabilities of globular proteins, called the heteropolymer collapse (HPC) model. It assumes that protein stability predominantly arises from the collapse of heteropolymeric chains of nonpolar and polar amino acids in water. The burial of nonpolar groups is opposed by configurational entropies and by electrostatic repulsions when proteins are in acids or bases. Although the model neglects helical propensities, ion pairing and other specific interactions, side-chain entropies and packing interactions, and—in its present version—burial of polar monomers, it predicts at least qualitatively several general properties of protein stability, including the dependences on temperature, denaturants, pH, and salts and radii of denatured states. For apomyoglobin, it predicts the phase boundaries for the three stable states-native, highly unfolded, and compact denatured states, as functions of temperature, pH, and salt. The model goes beyond isomer counting for chain entropies and beyond the assumption that denatured states are highly solvated random flights. © 1995, Academic Press Inc.