Identifying antigen binding sites from Ab sequence

The ability of antibodies to differentiate between antigens has made them indispensable tools in numerous medical and biological applications. The attempt to identify the residues within antibodies that mediate antigen binding has become the focus of extensive research over the last few decades. It is widely assumed that antigen binding sites correspond to the so-called Complementarity Determining Regions (CDRs).
We analyzed all known antibody-antigen complexes and found that about 20% of the antigen binding sites fall outside the CDRs. We found that the vast majority of antigen binding residues fall within regions of structural consensus between antibodies. Furthermore, we show that these regions are organized along the sequence of the antibody and are identifiable from both sequence and structure.