arXiv:2601.03704cs.LGcs.AI2026-01

用结构数据训练序列模型,提升蛋白质结合亲和力预测精度。

Investigating Knowledge Distillation Through Neural Networks for Protein Binding Affinity Prediction

  • 用结构信息指导序列模型训练,实现知识迁移。
  • 序列模型性能提升:相关系数达0.481,误差2.488 kcal/mol。
  • 适合缺乏结构数据但需高精度预测的研究者使用。

预测蛋白质-蛋白质结合亲和力时,准确性和数据可用性之间存在权衡。实验解析的蛋白质结构稀缺,限制了基于结构的机器学习模型性能,尽管这类模型通常优于基于序列的方法。为克服这一限制,我们提出一种基于知识蒸馏的回归框架:训练时使用蛋白质结构数据,推理时仅需序列数据。该方法通过结合结合亲和力标签与中间特征表示,由结构感知教师网络指导序列型学生网络的联合训练。在非冗余的蛋白质-蛋白质结合亲和力基准数据集上采用留一复合物交叉验证(LOCO)评估。仅用序列的基线模型取得最高皮尔逊相关系数(P_r)0.375、均方根误差(RMSE)2.712 kcal/mol;基于结构的模型则达到P_r 0.512、RMSE 2.445 kcal/mol。蒸馏后的学生模型表现显著提升,获得P_r 0.481、RMSE 2.488 kcal/mol。误差分析进一步证实其预测一致性提高、偏差降低。随着更大规模数据集的出现,该方法有望缩小序列与结构模型间的性能差距,表明知识蒸馏是向序列预测器转移结构知识的有效手段。推断代码可从 https://github.com/wajidarshad/ProteinAffinityKD 获取。

原文摘要 · Abstract (English)

The trade-off between predictive accuracy and data availability makes it difficult to predict protein--protein binding affinity accurately. The lack of experimentally resolved protein structures limits the performance of structure-based machine learning models, which generally outperform sequence-based methods. In order to overcome this constraint, we suggest a regression framework based on knowledge distillation that uses protein structural data during training and only needs sequence data during inference. The suggested method uses binding affinity labels and intermediate feature representations to jointly supervise the training of a sequence-based student network under the guidance of a structure-informed teacher network. Leave-One-Complex-Out (LOCO) cross-validation was used to assess the framework on a non-redundant protein--protein binding affinity benchmark dataset. A maximum Pearson correlation coefficient (P_r) of 0.375 and an RMSE of 2.712 kcal/mol were obtained by sequence-only baseline models, whereas a P_r of 0.512 and an RMSE of 2.445 kcal/mol were obtained by structure-based models. With a P_r of 0.481 and an RMSE of 2.488 kcal/mol, the distillation-based student model greatly enhanced sequence-only performance. Improved agreement and decreased bias were further confirmed by thorough error analyses. With the potential to close the performance gap between sequence-based and structure-based models as larger datasets become available, these findings show that knowledge distillation is an efficient method for transferring structural knowledge to sequence-based predictors. The source code for running inference with the proposed distillation-based binding affinity predictor can be accessed at https://github.com/wajidarshad/ProteinAffinityKD.

蛋白预测知识蒸馏亲和力预测

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