arXiv:2505.20301q-bio.QMcs.LG2025-05被引 7

仅用序列预测抗体亲和力变化,快速高效且可解释。

Sequence-Only Prediction of Binding Affinity Changes: A Robust and Interpretable Model for Antibody Engineering

  • 基于序列信息构建交叉注意力回归模型,无需三维结构。
  • 在三个基准上表现优于传统方法,尤其对不确定结构鲁棒。
  • 注意力机制可定位关键影响残基,适合抗体设计人员使用。

抗体工程中提升抗体-抗原结合亲和力是关键挑战。传统实验成本高、耗时长。现有深度学习方法依赖高质量复合物结构,但实际中常不可得。为此,我们提出ProtAttBA,仅基于抗体-抗原复合物的序列信息预测结合亲和力变化。该模型先通过预训练学习蛋白序列模式,再利用标注数据进行监督训练,构建基于交叉注意力的回归器。我们在三个公开基准上评估了ProtAttBA,在不同条件下均表现优异,显著优于序列与结构基方法,尤其在复合物结构不明确时更具鲁棒性。值得注意的是,其注意力机制具备可解释性,能识别影响亲和力的关键残基。本工作提供了一种快速、低成本的计算工具,有望加速新型治疗性抗体的研发。

原文摘要 · Abstract (English)

A pivotal area of research in antibody engineering is to find effective modifications that enhance antibody-antigen binding affinity. Traditional wet-lab experiments assess mutants in a costly and time-consuming manner. Emerging deep learning solutions offer an alternative by modeling antibody structures to predict binding affinity changes. However, they heavily depend on high-quality complex structures, which are frequently unavailable in practice. Therefore, we propose ProtAttBA, a deep learning model that predicts binding affinity changes based solely on the sequence information of antibody-antigen complexes. ProtAttBA employs a pre-training phase to learn protein sequence patterns, following a supervised training phase using labeled antibody-antigen complex data to train a cross-attention-based regressor for predicting binding affinity changes. We evaluated ProtAttBA on three open benchmarks under different conditions. Compared to both sequence- and structure-based prediction methods, our approach achieves competitive performance, demonstrating notable robustness, especially with uncertain complex structures. Notably, our method possesses interpretability from the attention mechanism. We show that the learned attention scores can identify critical residues with impacts on binding affinity. This work introduces a rapid and cost-effective computational tool for antibody engineering, with the potential to accelerate the development of novel therapeutic antibodies.

抗体设计序列预测可解释性

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