Antibodies often target cognate ligand epitopes without reproducing ligand contacts

Summary

Antibodies often bind the same target region as a cognate ligand, and occasionally reproduce its detailed contacts (1). A PDB survey found antibody-ligand epitope overlap in about 4,500 of 5,800 structures containing a target with a cognate ligand. Across more than 7,600 antibody-target structures, only 150 reproduced ligand contacts at the residue level, although about 900 had physicochemically similar interactions.

See also

• Ligand-mimicry filtering improves epitope-targeted antibody discovery
• Subset of antigen residues contribute disproportionately to antibody binding affinity

1.

Abanades B, Lopez-Morales J, Tanasijevic I, Wagner C, Speck J, Fenn S, et al. Mimic antibodies: leveraging ligand mimicry for epitope-targeted antibody discovery. mAbs. 2026;18(1):2719289. Available from: https://doi.org/10.1080/19420862.2026.2719289