Protein-protein interactions: additivity of the free energies of association of amino acid residues

Additivity of contributions to the free energies of association of ovomucoid third domain inhibitors with elastase, chymotrypsin and subtilisin (Laskowski, 1980; Laskowski et al., 1981, 1983; Empie & Laskowski, 1982) is fully demonstrated by applying the mathematical method of Free and Wilson (1964) for calculating the effects of substitutions in a family of drugs. Also demonstrated is the ability to predict the activity of third domain sequences. Sensitive regions in the contact area of inhibitor and enzyme are mapped, and a sequence is suggested for a new, more powerful and selective ovomucoid third domain inhibitor of subtilisin.