ConTact: Contact-First Antibody CDR Design via Explicit Interface Reasoning
Authors: Mansoor Ahmed, Spencer VonBank, Nadeem Taj et al.
Summary
arXiv:2605. 21600v1 Announce Type: new Abstract: Computational antibody CDR design methods condition on antigen structure to generate binding loops, yet existing architectures conflate two fundamentally distinct sub-problems: identifying which CDR positions will contact the antigen, and selecting amino acids at those positions.
Relevance
Read next because ConTact: Contact-First Antibody CDR Design via Explicit Interface Reasoning overlaps with clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)", clean result "Leakage rate is a usable signal for recovering trigger-shaped phrases on Gaperon-1125-1B without knowing the hidden trigger itself (MODERATE confidence)", clean result "Language-mismatch LoRA SFT on Qwen2.5-7B leaks the trained completion language into bystander directives the model was never trained on, absent under same-language SFT (LOW confidence)". Matching terms: code, line, rate, binding, stage, position, model. Source: arxiv cs.LG (Machine Learning).
Threat model
Potential threat/caveat for clean result "LoRA persona trained on alone emits at 23.5% when a co-trained partner learns ..., vs 0% control on Qwen2.5-7B-Instruct (MODERATE confidence)": this item discusses bias.
Abstract
arXiv:2605.21600v1 Announce Type: new Abstract: Computational antibody CDR design methods condition on antigen structure to generate binding loops, yet existing architectures conflate two fundamentally distinct sub-problems: identifying which CDR positions will contact the antigen, and selecting amino acids at those positions. This conflation forces models to learn contact reasoning implicitly through uniform message passing, diluting antigen signal across all positions equally. We introduce ConTact, a contact-then-act architecture that explicitly decomposes CDR design into three cascaded stages: learning surface complementarity fingerprints, predicting CDR-antigen contacts, and injecting contact-gated antigen features into the sequence head. A distance-biased cross-attention module encodes geometric priors favoring spatial neighbors, while a contact-weighted cross-entropy loss concentrates gradient signal on binding-critical positions. On CHIMERA-Bench dataset, ConTact achieves the best structural quality (7% RMSD improvement over the next-best baseline), best epitope awareness (10% F1 score over GNN baselines), and competitive sequence recovery (AAR 0.38) among several CDR-H3 design baselines.