Gang Luo, Junkai Wang, Sizhe Zhang, Zhilin Zhu, Zhangli Lu, Min Li
To address these challenges, we propose AbAgKer, an antibody screening model leveraging pre-trained representations and biological prior guidance for antigen-antibody affinity and kinetics prediction. Specifically, we design a biological prior-guided feature fusion framework that integrates pseudo-structural epitope knowledge and CDR-specific attention mechanisms via a mixture-of-experts architecture to effectively capture complex binding landscapes. To mitigate data scarcity, we employ a semi-supervised learning strategy for data self-distillation, which significantly enhances affinity prediction performance. Additionally, we demonstrate that the interaction representations learned by AbAgKer can be effectively transferred to the data-scarce task of predicting dissociation rates via few-shot learning. Extensive experiments demonstrate that AbAgKer outperforms baseline models and exhibits strong generalization capabilities in antibody screening and drug residence time analysis.
MOTIVATION: The rapid advancement of generative artificial intelligence has enabled the high-throughput design of therapeutic antibody candidates. However, the precise evaluation of these candidates remains a significant challenge due to the scarcity of high-quality activity data and the structural flexibility of antibody complementarity-determining regions (CDRs).
RESULTS: To address these challenges, we propose AbAgKer, an antibody screening model leveraging pre-trained representations and biological prior guidance for antigen-antibody affinity and kinetics prediction. Specifically, we design a biological prior-guided feature fusion framework that integrates pseudo-structural epitope knowledge and CDR-specific attention mechanisms via a mixture-of-experts architecture to effectively capture complex binding landscapes. To mitigate data scarcity, we employ a semi-supervised learning strategy for data self-distillation, which significantly enhances affinity prediction performance. Additionally, we demonstrate that the interaction representations learned by AbAgKer can be effectively transferred to the data-scarce task of predicting dissociation rates via few-shot learning. Extensive experiments demonstrate that AbAgKer outperforms baseline models and exhibits strong generalization capabilities in antibody screening and drug residence time analysis.
AVAILABILITY AND IMPLEMENTATION: The source code and dataset are available at https://github.com/CSUBioGroup/AbAgKer and https://doi.org/10.5281/zenodo.19691211.