Identification and design of binding determinants in proteins.

Mutagenic analysis are described for probing and designing binding determinants of two different proteins. The first protein is an enzyme, subtilisin, for which structural models were available for the enzyme-substrate complex. The second protein is human growth hormone for which a structural model of its complex with receptor was not available. In both cases, it was possible to identify and engineer binding determinants that lead to large changes in affinity.