ANTIBODY-COMBINING SITES - EXTENDING THE NATURAL LIMITS

The antibody repertoire is very large with at least 10(9) different an tibody specificities, yet there are currently only 800 variable-region sequences known and <23 Fab structures deposited with the Brookhaven Protein Data Bank. To engineer the antibody-combining site rationally, we need to define the rules that govern antibody structure. To unders tand the process of antibody-antigen recognition, we need not only to predict complementary determining regions accurately, but to simulate accurately the interaction of antibody with antigen. We have made prog ress in the modeling of antibody-combining sites and in the simulation of antibody complex formation. The combination of these approaches wi ll allow us to extend the natural limits of antibody-combining sites i n a more rational manner.