GSAML-DTA: An interpretable drug-target binding affinity prediction model based on graph neural networks with self-attention mechanism and mutual information

Abstract

Identifying drug-target affinity (DTA) has great practical importance in the process of designing efficacious drugs for known diseases. Recently, numerous deep learning-based computational methods have been developed to predict drug-target affinity and achieved impressive performance. However, most of them construct the molecule (drug or target) encoder without considering the weights of features of each node (atom or residue). Besides, they generally combine drug and target representations directly, which may contain irrelevant-task information. In this study, we develop GSAML-DTA, an interpretable deep learning framework for DTA prediction. GSAML-DTA integrates a self-attention mechanism and graph neural networks (GNNs) to build representations of drugs and target proteins from the structural information. In addition, mutual information is introduced to filter out redundant information and retain relevant information in the combined representations of drugs and targets. Extensive experimental results demonstrate that GSAML-DTA outperforms state-of-the-art methods for DTA prediction on two benchmark datasets. Furthermore, GSAML-DTA has the interpretation ability to analyze binding atoms and residues, which may be conducive to chemical biology studies from data. Overall, GSAML-DTA can serve as a powerful and interpretable tool suitable for DTA modelling.