arXiv:2512.22007cs.LG2025-12

仅用氨基酸序列预测抗体-抗原亲和力,精度超现有方法。

DuaDeep-SeqAffinity: Dual-Stream Deep Learning Framework for Sequence-Only Antigen-Antibody Affinity Prediction

  • 双流架构融合局部特征与全局上下文,基于ESM-2嵌入
  • 在真实数据上达到0.688的皮尔逊相关系数,优于结构依赖模型
  • 无需3D结构,适合大规模抗体筛选,加速药物研发

预测抗原与抗体之间的结合亲和力是药物发现和疫苗开发的基础。传统计算方法常依赖实验测定的三维结构,但这类结构稀缺且获取成本高。本文提出DuaDeep-SeqAffinity,一种仅基于氨基酸序列的深度学习框架,采用双流混合架构。该方法利用预训练的ESM-2蛋白语言模型嵌入,结合一维卷积神经网络(CNN)捕捉局部基序,以及Transformer编码器建模全局上下文。随后通过融合模块整合多维度特征,并送入全连接网络进行最终亲和力回归。实验表明,DuaDeep-SeqAffinity显著优于单一组件及现有最先进(SOTA)方法:皮尔逊相关系数达0.688,决定系数R²为0.460,均方根误差(RMSE)为0.737,超越单分支模型ESM-CNN与ESM-Transformer。尤为突出的是,模型在未见数据上的曲线下面积(AUC)达0.890,超过多数序列仅模型,甚至优于结构-序列混合模型。结果证明,高质量的序列嵌入可捕获原本需依赖结构建模的关键结合模式。该方法摆脱对3D结构的依赖,为海量序列库的高通量筛选提供高效可扩展的解决方案,大幅加速治疗靶点发现流程。

原文摘要 · Abstract (English)

Predicting the binding affinity between antigens and antibodies is fundamental to drug discovery and vaccine development. Traditional computational approaches often rely on experimentally determined 3D structures, which are scarce and computationally expensive to obtain. This paper introduces DuaDeep-SeqAffinity, a novel sequence-only deep learning framework that predicts affinity scores solely from their amino acid sequences using a dual-stream hybrid architecture. Our approach leverages pre-trained ESM-2 protein language model embeddings, combining 1D Convolutional Neural Networks (CNNs) for local motif detection with Transformer encoders for global contextual representation. A subsequent fusion module integrates these multi-faceted features, which are then passed to a fully connected network for final score regression. Experimental results demonstrate that DuaDeep-SeqAffinity significantly outperforms individual architectural components and existing state-of-the-art (SOTA) methods. DuaDeep achieved a superior Pearson correlation of 0.688, an R^2 of 0.460, and a Root Mean Square Error (RMSE) of 0.737, surpassing single-branch variants ESM-CNN and ESM-Transformer. Notably, the model achieved an Area Under the Curve (AUC) of 0.890, outperforming sequence-only benchmarks and even surpassing structure-sequence hybrid models. These findings prove that high-fidelity sequence embeddings can capture essential binding patterns typically reserved for structural modeling. By eliminating the reliance on 3D structures, DuaDeep-SeqAffinity provides a highly scalable and efficient solution for high-throughput screening of vast sequence libraries, significantly accelerating the therapeutic discovery pipeline.

亲和力预测深度学习抗体设计序列模型

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