# Antigen-specific Antibody Multi-modal Foundation Model for Functional Antibody Design

arXiv: https://arxiv.org/abs/2607.20057 · HTML: https://mlsanity.com/paper/2607.20057/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 33 of its 75 references that are in the map.
- First posted on arXiv 22 Jul 2026.

## Builds on (most cited first, 30 of 33)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Direct Preference Optimization: Your Language Model is Secretly a Reward Model](https://mlsanity.com/paper/2305.18290/) (2023)
- [Visual Instruction Tuning](https://mlsanity.com/paper/2304.08485/) (2023)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Parameter-Efficient Transfer Learning for NLP](https://mlsanity.com/paper/1902.00751/) (2019)
- [SimPO: Simple Preference Optimization with a Reference-Free Reward](https://mlsanity.com/paper/2405.14734/) (2024)
- [A General Theoretical Paradigm to Understand Learning from Human Preferences](https://mlsanity.com/paper/2310.12036/) (2023)
- [KTO: Model Alignment as Prospect Theoretic Optimization](https://mlsanity.com/paper/2402.01306/) (2024)
- [Iterative Reasoning Preference Optimization](https://mlsanity.com/paper/2404.19733/) (2024)
- [Smaug: Fixing Failure Modes of Preference Optimisation with DPO-Positive](https://mlsanity.com/paper/2402.13228/) (2024)
- [Video Understanding with Large Language Models: A Survey](https://mlsanity.com/paper/2312.17432/) (2023)
- [LLaVA-Plus: Learning to Use Tools for Creating Multimodal Agents](https://mlsanity.com/paper/2311.05437/) (2023)
- [Protein Representation Learning by Geometric Structure Pretraining](https://mlsanity.com/paper/2203.06125/) (2022)
- [ProGen2: Exploring the Boundaries of Protein Language Models](https://mlsanity.com/paper/2206.13517/) (2022)
- [Direct Preference Optimization with an Offset](https://mlsanity.com/paper/2402.10571/) (2024)
- [Iterative Refinement Graph Neural Network for Antibody Sequence-Structure Co-design](https://mlsanity.com/paper/2110.04624/) (2021)
- [Conditional Antibody Design as 3D Equivariant Graph Translation](https://mlsanity.com/paper/2208.06073/) (2022)
- [Structure-informed Language Models Are Protein Designers](https://mlsanity.com/paper/2302.01649/) (2023)
- [DPLM-2: A Multimodal Diffusion Protein Language Model](https://mlsanity.com/paper/2410.13782/) (2024)
- [Deciphering antibody affinity maturation with language models and weakly supervised learning](https://mlsanity.com/paper/2112.07782/) (2021)
- [Cal-DPO: Calibrated Direct Preference Optimization for Language Model Alignment](https://mlsanity.com/paper/2412.14516/) (2024)
- [End-to-End Full-Atom Antibody Design](https://mlsanity.com/paper/2302.00203/) (2023)
- [TIS-DPO: Token-level Importance Sampling for Direct Preference Optimization With Estimated Weights](https://mlsanity.com/paper/2410.04350/) (2024)
- [AbDiffuser: Full-Atom Generation of in vitro Functioning Antibodies](https://mlsanity.com/paper/2308.05027/) (2023)
- [Antigen-Specific Antibody Design via Direct Energy-based Preference Optimization](https://mlsanity.com/paper/2403.16576/) (2024)
- [ProteinBench: A Holistic Evaluation of Protein Foundation Models](https://mlsanity.com/paper/2409.06744/) (2024)
- [Sce2DriveX: A Generalized MLLM Framework for Scene-to-Drive Learning](https://mlsanity.com/paper/2502.14917/) (2025)
- [AIC MLLM: Autonomous Interactive Correction MLLM for Robust Robotic Manipulation](https://mlsanity.com/paper/2406.11548/) (2024)
- [Inverse folding for antibody sequence design using deep learning](https://mlsanity.com/paper/2310.19513/) (2023)

## Abstract (arXiv)

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.