POTENTIAL USE OF ADDITIVITY OF MUTATIONAL EFFECTS IN SIMPLIFYING PROTEIN ENGINEERING

The problem of rationally engineering protein molecules can be simplif ied where effects of mutations on protein function are additive. Cryst al structures of single and double mutants in the hydrophobic core of gene V protein indicate that structural and functional effects of core mutations are additive when the regions structurally influenced by th e mutations do not substantially overlap. These regions of influence c an provide a simple basis for identifying sets of mutations that will show additive effects.