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CAME-AB: Cross-Modality Attention with Mixture-of-Experts for Antibody Binding Site Prediction

8 September 2025
Hongzong Li
Jiahao Ma
Zhanpeng Shi
Rui Xiao
Fanming Jin
Ye-Fan Hu
Hangjun Che
ArXiv (abs)PDFHTML
Main:9 Pages
4 Figures
Bibliography:3 Pages
6 Tables
Appendix:2 Pages
Abstract

Antibody binding site prediction plays a pivotal role in computational immunology and therapeutic antibody design. Existing sequence or structure methods rely on single-view features and fail to identify antibody-specific binding sites on the antigens. In this paper, we propose \textbf{CAME-AB}, a novel Cross-modality Attention framework with a Mixture-of-Experts (MoE) backbone for robust antibody binding site prediction. CAME-AB integrates five biologically grounded modalities, including raw amino acid encodings, BLOSUM substitution profiles, pretrained language model embeddings, structure-aware features, and GCN-refined biochemical graphs, into a unified multimodal representation. To enhance adaptive cross-modal reasoning, we propose an \emph{adaptive modality fusion} module that learns to dynamically weight each modality based on its global relevance and input-specific contribution. A Transformer encoder combined with an MoE module further promotes feature specialization and capacity expansion. We additionally incorporate a supervised contrastive learning objective to explicitly shape the latent space geometry, encouraging intra-class compactness and inter-class separability. To improve optimization stability and generalization, we apply stochastic weight averaging during training. Extensive experiments on benchmark antibody-antigen datasets demonstrate that CAME-AB consistently outperforms strong baselines on multiple metrics, including Precision, Recall, F1-score, AUC-ROC, and MCC. Ablation studies further validate the effectiveness of each architectural component and the benefit of multimodal feature integration. The model implementation details and the codes are available on this https URL

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