Summary
Blinded prospective antibody-design methods performed better at affinity maturation when HCDR3 was held fixed than at HCDR3-cluster ranking or out-of-library CDR design (1). The fixed-HCDR3 affinity-maturation task produced several developable antibodies with affinities below 100 pM. These successes were exceptions that did not transfer across tasks: nearly every method underperformed random selection in HCDR3-cluster ranking, and out-of-library CDR design was highly variable.
See also
- CDRH3 has most contacts with antigen
- CDRH3 is necessary but insufficient to guarantee binding to a particular epitope
- De novo antibody design
1.
Erasmus MF, Bedinger D, Hopkins E, Ferguson G, Strickler J, Graff CP, et al. A blinded, prospective benchmark of in silico antibody discovery anchored to experimental affinity and developability. Nature Biotechnology. 2026; Available from: https://doi.org/10.1038/s41587-026-03238-6