论文标题

翻新:图形搜索的逆合合成计划

RetroGraph: Retrosynthetic Planning with Graph Search

论文作者

Xie, Shufang, Yan, Rui, Han, Peng, Xia, Yingce, Wu, Lijun, Guo, Chenjuan, Yang, Bin, Qin, Tao

论文摘要

旨在找到合成靶分子的反应途径的递归合成计划在化学和药物发现中起着重要作用。此任务通常被建模为搜索问题。最近,数据驱动的方法吸引了许多研究兴趣,并显示了反递归计划的有希望的结果。我们观察到,在搜索过程中多次访问过相同的中间分子,并且通常在先前基于树的方法(例如,或树搜索,蒙特卡洛树搜索)中独立处理。这样的冗余使搜索过程效率低下。我们提出了一种基于图的搜索策略,以消除任何中间分子的冗余探索。由于在图上搜索比在树上搜索更为复杂,因此我们进一步采用图形神经网络来指导图形搜索。同时,我们的方法可以在图中搜索一批目标,并在基于树的搜索方法中删除目标间重复。两个数据集的实验结果证明了我们方法的有效性。尤其是在广泛使用的USPTO基准测试中,我们将搜索成功率提高到99.47%,以2.6分提高了先前的最新性能。

Retrosynthetic planning, which aims to find a reaction pathway to synthesize a target molecule, plays an important role in chemistry and drug discovery. This task is usually modeled as a search problem. Recently, data-driven methods have attracted many research interests and shown promising results for retrosynthetic planning. We observe that the same intermediate molecules are visited many times in the searching process, and they are usually independently treated in previous tree-based methods (e.g., AND-OR tree search, Monte Carlo tree search). Such redundancies make the search process inefficient. We propose a graph-based search policy that eliminates the redundant explorations of any intermediate molecules. As searching over a graph is more complicated than over a tree, we further adopt a graph neural network to guide the search over graphs. Meanwhile, our method can search a batch of targets together in the graph and remove the inter-target duplication in the tree-based search methods. Experimental results on two datasets demonstrate the effectiveness of our method. Especially on the widely used USPTO benchmark, we improve the search success rate to 99.47%, advancing previous state-of-the-art performance for 2.6 points.

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