Influence of interior packing and hydrophobicity on the stability of a protein.

Protein interiors contain many tightly packed apolar atoms in a nearly crystalline state. Both shielding of apolar atoms from solvent and efficient interior packing arrangements affect protein stability, but their relative importance is unclear. To separate these effects, the stabilities of wild-type and mutant gene V proteins from bacteriophage fl were studied by measuring resistance to denaturation. The effects of subtle interior packing changes, both separate from and combined with changes in buried side chain hydrophobicity, were measured. For the interior apolar-to-apolar substitutions studied, the two effects were of the same magnitude and alteration of packing without accompanying hydrophobicity changes substantially destabilized the protein.