Knowledge graph-enhanced molecular contrastive learning with functional prompt

Yin Fang, Qiang Zhang, Ningyu Zhang, Zhuo Chen, Xiang Zhuang, Xin Shao, Xiaohui Fan, Huajun Chen

Abstract: Deep learning models can accurately predict molecular properties and help making the search for potential drug candidates faster and more efficient. Many existing methods are purely data driven, focusing on exploiting the intrinsic topology and construction rules of molecules without any chemical prior information. The high data dependency makes them difficult to generalize to a wider chemical space and leads to a lack of interpretability of predictions. Here, to address this issue, we introduce a chemical element-oriented knowledge graph to summarize the basic knowledge of elements and their closely related functional groups. We further propose a method for knowledge graph-enhanced molecular contrastive learning with functional prompt (KANO), exploiting external fundamental domain knowledge in both pre-training and fine-tuning. Specifically, with element-oriented knowledge graph as a prior, we first design an element-guided graph augmentation in contrastive-based pre-training to explore microscopic atomic associations without violating molecular semantics. Then, we learn functional prompts in fine-tuning to evoke the downstream task-related knowledge acquired by the pre-trained model. Extensive experiments show that KANO outperforms state-of-the-art baselines on 14 molecular property prediction datasets and provides chemically sound explanations for its predictions. This work contributes to more efficient drug design by offering a high-quality knowledge prior, interpretable molecular representation and superior prediction performance. Deep learning can be used to predict molecular properties, but such methods usually need a large amount of data and are hard to generalize to different chemical spaces. To provide a useful primer for deep learning models models, Fang and colleagues use contrastive learning and a knowledge graph based on the Periodic Table and Wikipedia pages on chemical functional groups.