ReduMixDTI: Prediction of Drug-Target Interaction with Feature Redundancy Reduction and Interpretable Attention Mechanism.

Abstract

Identifying drug-target interactions (DTIs) is essential for drug discovery and development. Existing deep learning approaches to DTI prediction often employ powerful feature encoders to represent drugs and targets holistically, which usually cause significant redundancy and noise by neglecting the restricted binding regions. Furthermore, many previous DTI networks ignore or simplify the complex intermolecular interaction process involving diverse binding types, which significantly limits both predictive ability and interpretability. We propose ReduMixDTI, an end-to-end model that addresses feature redundancy and explicitly captures complex local interactions for DTI prediction. In this study, drug and target features are encoded by using graph neural networks and convolutional neural networks, respectively. These features are refined from channel and spatial perspectives to enhance the representations. The proposed attention mechanism explicitly models pairwise interactions between drug and target substructures, improving the model's understanding of binding processes. In extensive comparisons with seven state-of-the-art methods, ReduMixDTI demonstrates superior performance across three benchmark data sets and external test sets reflecting real-world scenarios. Additionally, we perform comprehensive ablation studies and visualize protein attention weights to enhance the interpretability. The results confirm that ReduMixDTI serves as a robust and interpretable model for reducing feature redundancy, contributing to advances in DTI prediction.