arXiv:2412.07778q-bio.QMcs.LG2024-12被引 5

用多通道网络预测药物与靶点结合,提升准确率并解释结合位点。

MIN: Multi-channel Interaction Network for Drug-Target Interaction with Protein Distillation

  • 设计多通道交互模块融合结构相关与无关信息,捕捉多层次结合模式。
  • 在多个公开数据集上超越现有方法,关键残基选择与实际结合口袋高度重合。
  • 适用于药物研发中的靶点预测与可解释性分析,适合生物信息学研究者。

传统药物发现耗时且依赖专业知识。随着实验积累的药物-靶点相互作用(DTI)数据增多,利用机器学习识别药物与靶蛋白间的模式成为可能。本文提出多通道交互网络(MIN),由表征学习模块和多通道交互模块构成。前者通过C-Score Predictor辅助筛选关键残基,提升准确性并降低噪声;后者包含无结构、有结构和扩展混合三通道,实现多层级交互模式互补。同时采用对比学习统一异构数据表示。在多个公开数据集上的实验表明,MIN优于现有强方法。案例分析显示C-Score Predictor选出的残基与实际结合口袋高度重合,验证了模型可解释性。结果表明MIN不仅是高效预测工具,也为蛋白质结合位点预测提供了新视角。

原文摘要 · Abstract (English)

Traditional drug discovery processes are both time-consuming and require extensive professional expertise. With the accumulation of drug-target interaction (DTI) data from experimental studies, leveraging modern machine-learning techniques to discern patterns between drugs and target proteins has become increasingly feasible. In this paper, we introduce the Multi-channel Interaction Network (MIN), a novel framework designed to predict DTIs through two primary components: a representation learning module and a multi-channel interaction module. The representation learning module features a C-Score Predictor-assisted screening mechanism, which selects critical residues to enhance prediction accuracy and reduce noise. The multi-channel interaction module incorporates a structure-agnostic channel, a structure-aware channel, and an extended-mixture channel, facilitating the identification of interaction patterns at various levels for optimal complementarity. Additionally, contrastive learning is utilized to harmonize the representations of diverse data types. Our experimental evaluations on public datasets demonstrate that MIN surpasses other strong DTI prediction methods. Furthermore, the case study reveals a high overlap between the residues selected by the C-Score Predictor and those in actual binding pockets, underscoring MIN's explainability capability. These findings affirm that MIN is not only a potent tool for DTI prediction but also offers fresh insights into the prediction of protein binding sites.

药物发现蛋白结合可解释性

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