Benchmark on Drug Target Interaction Modeling from a Structure Perspective

Abstract: The prediction modeling of drug-target interactions is crucial to drug discovery and design, which has seen rapid advancements owing to deep learning technologies. Recently developed methods, such as those based on graph neural networks (GNNs) and Transformers, demonstrate exceptional performance across various datasets by effectively extracting structural information. However, the benchmarking of these novel methods often varies significantly in terms of hyperparameter settings and datasets, which limits algorithmic progress. In view of these, we conduct a comprehensive survey and benchmark for drug-target interaction modeling from a structure perspective, via integrating tens of explicit (i.e., GNN-based) and implicit (i.e., Transformer-based) structure learning algorithms. To this end, we first unify the hyperparameter setting within each class of structure learning methods. Moreover, we conduct a macroscopical comparison between these two classes of encoding strategies as well as the different featurization techniques that inform molecules' chemical and physical properties. We then carry out the microscopical comparison between all the integrated models across the six datasets, via comprehensively benchmarking their effectiveness and efficiency. Remarkably, the summarized insights from the benchmark studies lead to the design of model combos. We demonstrate that our combos can achieve new state-of-the-art performance on various datasets associated with cost-effective memory and computation. Our code is available at \hyperlink{https://github.com/justinwjl/GTB-DTI/tree/main}{https://github.com/justinwjl/GTB-DTI/tree/main}.