A unified survey on drug-target interaction and binding affinity prediction: Models, representations, and challenges

Drug discovery is a complex and systematic process aimed at finding new treatment methods that can prevent or treat specific diseases. Accurately predicting the interaction and binding affinity between drugs and targets is one of the key steps in modern drug development. Although traditional experimental methods are accurate, they are difficult to meet the efficiency requirements of current drug development due to high costs, low throughput, and high failure rates. In contrast, computational prediction methods are gradually becoming an indispensable auxiliary tool that can not only significantly shorten the research and development cycle and reduce experimental costs, but also improve the success rate of candidate drug screening. This review focuses on the research of drug-target interaction (DTI) and drug-target binding affinity (DTA), and systematically reviews the relevant research progress. Distinct from existing reviews, we treat large pre-trained model-based approaches as an independent paradigm, rather than subsuming them under conventional sequence- or structure-based models. The article first outlines commonly used resources and methods from the perspective of data and representation, and the computational definition of drug target prediction problem was clarified. On this basis, we have summarized the development path of computational models, from early similarity and feature driven models, to matrix decomposition, network analysis, sequence and structure modeling, and then to the emergence of large-scale pre-trained models in recent years, forming a relatively complete technological evolution path. The article also summarizes the experience at the experimental level, such as the selection of evaluation indicators, handling of cold start scenarios, design of case studies, and analysis of model interpretability. Finally, we synthesize key challenges and identify several directions for future research.