UniTact: Sequence-Only Unified Antibody–Antigen Interaction Modeling for Contact and Interface Prediction

Identifying antibody–antigen interfaces is essential for understanding immune recognition and the effects of antigen mutations. Given a binding antibody–antigen pair, however, their relative binding geometry is unknown from sequences or monomer structures alone, making the joint prediction of antibody-side paratopes, antigen-side epitopes, and residue-level contacts challenging. Existing approaches either rely on complex structures or focus on individual interface tasks, and residue-pair predictions can be dominated by marginal residue preferences rather than partner-specific interactions. We introduce UniTact, a unified framework that predicts paratopes, epitopes, and residue-level contacts from a shared antibody–antigen contact surface. The model takes sequences as its only raw input and incorporates separately predicted monomer structures to construct interaction representations through intrachain encoding, cross-attention, and pair updates. We further introduce a double-centering strategy on pair scores to reduce additive row and column effects, making the readouts more sensitive to pair-specific variation. On SAbDab2, our method achieves an epitope AUPRC of 0.2232, improving over the sequence-based baseline SPPIDER-seq (0.2034), while obtaining paratope AUROC of 0.9561 and contact AUROC of 0.9203. Further score decomposition, controlled experiments, and split-based analyses help characterize the sources of residue-level bias and clarify the remaining challenges of pair-specific contact prediction.