HMG-DTI: a drug-target interaction prediction framework combining Hierarchical Molecular Graphs and improved Convolutional Block Attention Module

Abstract

Drug-target interactions (DTIs) are fundamental to understanding the therapeutic mechanisms of drugs, yet accurately predicting these interactions remains a significant challenge in drug discovery. Current computational approaches often fail to capture essential molecular motifs and spatial information of proteins, limiting their effectiveness, particularly when encountering proteins or compounds absent in the training datasets. To address these limitations, we propose mHMG-DTI, a novel framework that leverages an improved Convolutional Block Attention Module (iCBAM) for enhanced protein feature extraction and modified Hierarchical Molecular Graphs (mHMGs) for comprehensive molecular encoding. This hierarchical approach not only captures detailed local structures and broader connectivity patterns but also incorporates guiding knowledge to improve feature representation. Across a total of 16 experimental evaluations on four benchmark datasets spanning both classification and regression tasks, mHMG-DTI surpasses existing baseline models in 11 cases. These results highlight the potential of mHMG-DTI to enhance DTI prediction accuracy, thereby accelerating the drug discovery process and providing valuable insights into drug resistance and side effect mechanisms. Contactzeruiyang2-c@my.cityu.edu.hk