Contrastive learning enables epitope overlap predictions for targeted antibody discovery.

ABSTRACT: Computational epitope prediction remains an unmet need for therapeutic antibody development. We present three complementary approaches for predicting epitope relationships from antibody sequences. First, by analyzing approximately 18 million antibody pairs targeting around 250 protein families, we establish that over 70% of heavy-chain complementarity-determining region 3 (CDRH3) sequence identity among antibodies sharing both V genes reliably predicts overlapping epitopes. Second, we develop a supervised contrastive fine-tuning framework for antibody large language models that enriches embeddings with epitope information. Applied to SARS-CoV-2 receptor-binding-domain antibodies, this approach achieves 97% total accuracy in predicting high levels of structural overlap. Third, we create AbL

SUBMITTER: Holt CM 

PROVIDER: S-EPMC12921510 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature