关键词: 药物逆合成, 门控图卷积神经网络, 主动采样, 有机化学反应, 原子隐藏特征

Abstract: Under the development of modern pharmaceutical and computer technologies, using artificial intelligence technology to accelerate drug development progress has become a research hotspot. And efficient prediction of organic reaction products is a key issue in drug retrosynthesis path planning. Concerning the problem of uneven distribution of chemical reaction types in the sample dataset, an Active Sampling-training Gated Graph Convolutional Neural-network (ASGGCN) model was proposed. Firstly, the SMILES (Simplified Molecular Input Line Entry Specification) codes of the chemical reactants were input into the model, and the location of the reaction center was predicted through Gated Graph Convolutional Neural-network (GGCN) and attention mechanism. Then, according to chemical constraint conditions and the candidate reaction centers, the possible chemical bond combinations were enumerated to generate candidate reaction products. After that, the gated graph convolutional difference network was used to rank the candidate products and obtain the final reaction product. Compared with the traditional graph convolutional network, the gated graph convolutional network has three weight parameter matrices and fuse the information through gating, so it can obtain more abundant atom hidden feature information. At the same time, the gated graph convolutional network is trained by active sampling, which can take into account both the analysis abilities of poor samples and ordinary samples. Experimental results show that the Top-1 prediction accuracy of the reaction product of the proposed model reaches 87.2%, which is increased by 1.6 percentage points compared to the accuracy of WLDN (Weisfeiler-Lehman Difference Network) model, illustrating that the organic reaction products can be predicted more accurately by the proposed model.

Key words: drug retrosynthesis, Gated Graph Convolutional Neural-network (GGCN), active sampling, organic reaction, atom hidden feature