Mapping discontinuous antibody epitopes to reveal protein structure and changes in structure related to function

Abstract

We are developing a new method for protein structure determination that overcomes limitations in traditional methods, such as x-ray crystallography or nuclear magnetic resonance, and requires about a thousandfold less protein. The method, called antibody imprinting, uses antibodies against target proteins and random peptide probe libraries to map the epitopes of antibody binding sites on target proteins. Virtually all known antibody epitopes are highly discontinuous and are "assembled" by folding together regions of the protein that are far apart in the primary sequence. The antibody imprinting method seeks to rapidly and efficiently "mine" the antibody epitope information to reveal the structure of the target proteins.