Deciphering antibody-protein antigen recognition is of fundamental and practical significance. We constructed an antibody structural dataset, partitioned it into human and murine subgroups, and compared it with non-antibody protein-protein complexes. We investigated the physico-chemical properties of regions on and away from the antibody-antigen interfaces, including net-charge, overall antibody charge distributions and their potential role in antigen interaction. We observed that amino acid preference in antibody-protein antigen recognition is entropy driven, with residues having low side-chain entropy appearing to compensate for the high backbone entropy in interaction with protein antigens. Antibodies prefer charged and polar antigen residues, and bridging water molecules. They also prefer positive net-charge, presumably to promote interaction with negatively charged protein antigens, which are common in proteomes. Antibody-antigen interfaces are mostly negatively charged with dominant contribution of Asp and a positively charged region. Here we describe some features of antibody-antigen interfaces and of Fab domains as compared to non-antibody protein-protein interactions. The distributions of interface residues in human and murine antibodies do not differ significantly. Overall, our results provide not only a local but a global anatomy of antibody structures.
展开▼
