Polar group burial contributes more to protein stability than nonpolar group burial

On the basis of studies of Asn to Ala mutants, the gain in stability from b urying amide groups that are hydrogen bonded to peptide groups is 80 cal/(m ol Angstrom (3)). On the basis of similar studies of Leu to Ala and Ile to Val mutants, the gain in stability from burying -CH2- groups is 50 cal/(mol Angstrom (3)). Thus, the burial of an amide group contributes more to prot ein stability than the burial of an equivalent volume of -CH2-groups. Apply ing these results to folded proteins leads to the surprising conclusion tha t peptide group burial makes a larger contribution to protein stability tha n nonpolar side chain burial. Several studies have shown that the desolvati on penalty for burying peptide groups is considerably smaller than generall y thought. This suggests that the hydrogen bonding and van der Waals intera ctions of peptide groups in the tightly packed interior of folded protein a re mon favorable than similar interactions with water in the unfolded prote in.