Subgraph-based Self-Supervised Learning Framework for Enzymatic Reaction Feasibility Prediction

Feng Yang, Juan Liu, Qiang Zhang, Zhihui Yang, Jianghang Liu, Guangsheng Wu

Abstract: Enzymatic Reaction feasibility prediction is used to determine whether the reaction generated by computational methods can actually occur, which can effectively reduce the complexity of synthetic pathway design. Existing methods often use SMILES or molecular fingerprints to represent molecules, resulting in a lack of molecular structural information. Although some GNNs have been leveraged to solve this problem, the complexity of the intra and inter-substructures interactions of molecules in microorganisms makes it difficult for traditional GNNs to accurately model it. To address these problems, we propose a subgraph-based self-supervised learning framework to predict the feasibility of enzymatic reactions. Specifically, we first propose a subgraph-based two-branch graph neural network. This network leverages the atom graph and substructure graph of a molecule to thoroughly capture its structural and semantic information. Besides, a subgraph interaction module is designed to facilitate the full integration of features. Subsequently, we propose a domain knowledge-guided self-supervised learning task, utilizing molecular fingerprints and substructures to capture the consistency between them effectively. The experimental results show that the proposed method outperforms existing state-ofthe-art methods significantly on all datasets.