Paper Detail
Xiaoliang Shi, Zichen Wang, Runze Ma, Zhongyue Zhang, Shuangjia Zheng
Antibodies are essential proteins that play a central role in immune recognition by binding specific antigen molecules. Although recent protein language models have enabled progress in single-chain protein modeling and generation, they often fall short in antigen-specific antibody design, where effective modeling requires explicit pairing between antibody and antigen, particularly at the epitope level. To address these limitations, we introduce AAMFM, an Antigen-specific Antibody Multimodal Foundation Model that learns unified representations of antibody sequences and structures conditioned on antigen context. AAMFM incorporates rich antigen information including geometric interfaces and epitope annotations via a cross-modal adapter, enabling joint modeling of antibody-antigen interactions in a shared latent space. To further guide the model toward functional relevance, we fine-tune AAMFM using Calibrated Direct Preference Optimization (Cal-DPO), leveraging preference signals extracted from a strong structural prior to align learning with binding-specific objectives. Extensive experiments demonstrate that AAMFM achieves state-of-the-art performance in functional antibody design, revealing its potential for antigen-specific antibody engineering. Our code is available at https://github.com/XL-S224/AAMFM.
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@article{shi2026antigen,
title = {Antigen-specific Antibody Multi-modal Foundation Model for Functional Antibody Design},
author = {Xiaoliang Shi and Zichen Wang and Runze Ma and Zhongyue Zhang and Shuangjia Zheng},
year = {2026},
abstract = {Antibodies are essential proteins that play a central role in immune recognition by binding specific antigen molecules. Although recent protein language models have enabled progress in single-chain protein modeling and generation, they often fall short in antigen-specific antibody design, where effective modeling requires explicit pairing between antibody and antigen, particularly at the epitope level. To address these limitations, we introduce AAMFM, an Antigen-specific Antibody Multimodal Foun},
url = {https://arxiv.org/abs/2607.20057},
keywords = {q-bio.BM, cs.LG},
eprint = {2607.20057},
archiveprefix = {arXiv},
}
{}