Protein Engineering: Methods and Applications

This chapter provides examples of different protein engineering techniques to elucidate structure-function relationships. These are illustrated with case studies describing the optimization of therapeutic proteins for specificity and affinity. The chapter describes how protein engineering has been used to modulate immunoglobulin G (IgG) serum half-life either through Fc engineering or via pH-dependent antigen binding. Rational design relies on the structural analysis of proteins to identify regions for introducing mutations to improve desirable traits such as affinity, stability, specificity, and enzyme activity. Rational design approaches have been successfully applied in the generation of therapeutic enzymes with new or improved activities. Rational design can be applied to engineer therapeutic antibodies for higher affinity or improved specificity. A strong relationship exists between the efficacy of some therapeutic antibodies and their effector functions. Engineering strategies to augment effector functions are of great interest to improve the efficacy of antibody therapy.