An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants

Structure. 2021 Jun 3;29(6):606-621.e5. doi: 10.1016/j.str.2021.01.005. Epub 2021 Feb 3.


Accurate predictive modeling of antibody-antigen complex structures and structure-based antibody design remain major challenges in computational biology, with implications for biotherapeutics, immunity, and vaccines. Through a systematic search for high-resolution structures of antibody-antigen complexes and unbound antibody and antigen structures, in conjunction with identification of experimentally determined binding affinities, we have assembled a non-redundant set of test cases for antibody-antigen docking and affinity prediction. This benchmark more than doubles the number of antibody-antigen complexes and corresponding affinities available in our previous benchmarks, providing an unprecedented view of the determinants of antibody recognition and insights into molecular flexibility. Initial assessments of docking and affinity prediction tools highlight the challenges posed by this diverse set of cases, which includes camelid nanobodies, therapeutic monoclonal antibodies, and broadly neutralizing antibodies targeting viral glycoproteins. This dataset will enable development of advanced predictive modeling and design methods for this therapeutically relevant class of protein-protein interactions.

Keywords: affinity prediction; antibody design; biotherapeutics; monoclonal antibodies; nanobody; protein-protein docking; viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Antibodies / chemistry*
  • Antibodies / metabolism*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / metabolism
  • Antigen-Antibody Complex / chemistry
  • Antigens / chemistry*
  • Antigens / metabolism*
  • Benchmarking
  • Broadly Neutralizing Antibodies / chemistry
  • Broadly Neutralizing Antibodies / metabolism
  • Computational Biology / methods
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Conformation
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / metabolism
  • Software
  • Structure-Activity Relationship


  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antigen-Antibody Complex
  • Antigens
  • Broadly Neutralizing Antibodies
  • Single-Domain Antibodies