Improving Identification of Drug-Target Binding Sites Based on Structures of Targets Using Residual Graph Transformer Network.

Abstract

Improving identification of drug-target binding sites can significantly aid in drug screening and design, thereby accelerating the drug development process. However, due to challenges such as insufficient fusion of multimodal information from targets and imbalanced datasets, enhancing the performance of drug-target binding sites prediction models remains exceptionally difficult. Leveraging structures of targets, we proposed a novel deep learning framework, RGTsite, which employed a Residual Graph Transformer Network to improve the identification of drug-target binding sites. First, a residual 1D convolutional neural network (1D-CNN) and the pre-trained model ProtT5 were employed to extract the local and global sequence features from the target, respectively. These features were then combined with the physicochemical properties of amino acid residues to serve as the vertex features in graph. Next, the edge features were incorporated, and the residual graph transformer network (GTN) was applied to extract the more comprehensive vertex features. Finally, a fully connected network was used to classify whether the vertex was a binding site. Experimental results showed that RGTsite outperformed the existing state-of-the-art methods in key evaluation metrics, such as F1-score (F1) and Matthews Correlation Coefficient (MCC), across multiple benchmark datasets. Additionally, we conducted interpretability analysis for RGTsite through the real-world cases, and the results confirmed that RGTsite can effectively identify drug-target binding sites in practical applications.