The Role of Interior Side-Chain Packing in Protein Folding and Stability

Abstract

A nearly universal feature of the structures of globular proteins is a buried core consisting of hydrophobic side chains (Chothia, 1976). The favorable free-energy of transfer of these side chains from a solvent-accessible to solvent-inaccessible state is considered the major driving force for the folding of globular proteins in aqueous solution (Dill, 1990). The large hydrophobic, buried side chains are key determinants of protein structure and stability (Alber et al., 1987; Bowie et al, 1990; Shortle et al., 1990). These side chains tend to be tightly packed (Richards, 1974) and more rigid than the rest of the protein. Steric packing interactions involving these side chains may provide constraints for protein folding (Richards, 1974). The purpose of this review is to summarize the implications of recent experiments for the role of packing interactions in protein folding and stability.