Improving drug–target affinity prediction by adaptive self-supervised learning

Abstract

Computational drug-target affinity prediction is important for drug screening and discovery. Currently, self-supervised learning methods face two major challenges in drug-target affinity prediction. The first difficulty lies in the phenomenon of sample mismatch: self-supervised learning processes drug and target samples independently, while actual prediction requires the integration of drug-target pairs. Another challenge is the mismatch between the broadness of self-supervised learning objectives and the precision of biological mechanisms of drug-target affinity ( i.e ., the induced-fit principle). The former focuses on global feature extraction, while the latter emphasizes the importance of local precise matching. To address these issues, an adaptive self-supervised learning-based drug-target affinity prediction (ASSLDTA) was designed. ASSLDTA integrates a novel adaptive self-supervised learning (ASSL) module with a high-level feature learning network to extract the feature. The ASSL leverages a large amount of unlabeled training data to effectively capture low-level features of drugs and targets. Its goal is to maximize the retention of original feature information, thereby bridging the objective gap between self-supervised learning and drug-target affinity prediction and alleviating the sample mismatch problem. The high-level feature learning network, on the other hand, focuses on extracting effective high-level features for affinity prediction through a small amount of labeled data. Through this two-stage feature extraction design, each stage undertakes specific tasks, fully leveraging the advantages of each model while efficiently integrating information from different data sources, providing a more accurate and comprehensive solution for drug-target affinity prediction. In our experiments, ASSLDTA is much better than other deep methods, and the result of ASSLDTA is significantly increased by learning adaptive self-supervised learning-based features, which validates the effectiveness of our ASSLDTA.