论文标题

用于药物 - 靶标结合亲和力预测的远距离感知分子图注意网络

Distance-aware Molecule Graph Attention Network for Drug-Target Binding Affinity Prediction

论文作者

Zhou, Jingbo, Li, Shuangli, Huang, Liang, Xiong, Haoyi, Wang, Fan, Xu, Tong, Xiong, Hui, Dou, Dejing

论文摘要

准确地预测药物与蛋白质之间的结合亲和力是计算药物发现的重要步骤。由于图神经网络(GNN)在各种与图形相关的任务中取得了显着成功,因此GNN被认为是改善近年来结合亲和力预测的有前途的工具。但是,大多数现有的GNN结构只能编码药物和蛋白质的拓扑图结构,而无需考虑其原子之间的相对空间信息。尽管与其他图形数据集不同,例如社交网络和常识性知识图,但原子之间的相对空间位置和化学键对结合亲和力产生了重大影响。为此,在本文中,我们提出了一个针对药物靶向结合亲和力预测量身定制的远距离感知分子图注意网络(S-MAN)。作为一个专用解决方案,我们首先提出了一种编码机制,以将拓扑结构和空间位置信息整合到构造的袖珍配体图中。此外,我们提出了一种新型的边缘节点层次构型聚合结构,该结构具有边缘级聚集和节点级聚集。分层的细心聚集可以捕获原子之间的空间依赖性,并融合了位置增强的信息与能够区分原子之间多重空间关系的能力。最后,我们对两个标准数据集进行了广泛的实验,以证明S-MAN的有效性。

Accurately predicting the binding affinity between drugs and proteins is an essential step for computational drug discovery. Since graph neural networks (GNNs) have demonstrated remarkable success in various graph-related tasks, GNNs have been considered as a promising tool to improve the binding affinity prediction in recent years. However, most of the existing GNN architectures can only encode the topological graph structure of drugs and proteins without considering the relative spatial information among their atoms. Whereas, different from other graph datasets such as social networks and commonsense knowledge graphs, the relative spatial position and chemical bonds among atoms have significant impacts on the binding affinity. To this end, in this paper, we propose a diStance-aware Molecule graph Attention Network (S-MAN) tailored to drug-target binding affinity prediction. As a dedicated solution, we first propose a position encoding mechanism to integrate the topological structure and spatial position information into the constructed pocket-ligand graph. Moreover, we propose a novel edge-node hierarchical attentive aggregation structure which has edge-level aggregation and node-level aggregation. The hierarchical attentive aggregation can capture spatial dependencies among atoms, as well as fuse the position-enhanced information with the capability of discriminating multiple spatial relations among atoms. Finally, we conduct extensive experiments on two standard datasets to demonstrate the effectiveness of S-MAN.

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