论文标题

RETROGNN:通过图神经网络近似逆合合成,以进行新药物设计

RetroGNN: Approximating Retrosynthesis by Graph Neural Networks for De Novo Drug Design

论文作者

Liu, Cheng-Hao, Korablyov, Maksym, Jastrzębski, Stanisław, Włodarczyk-Pruszyński, Paweł, Bengio, Yoshua, Segler, Marwin H. S.

论文摘要

从头分子的产生通常会导致化学上不可行的分子。缓解此问题的一个自然想法是将搜索过程偏向更容易合成的分子,该分子使用代理进行合成可访问性。但是,使用当前可用的代理仍然会导致高度不切实际的化合物。我们研究了训练深图神经网络的可行性,以近似逆转录合成计划软件的输出,并用于偏向搜索过程。我们在基准上评估我们的方法,涉及搜索具有抗生素特性的药物样分子。与从锌数据库中枚举超过500万个现有分子相比,我们的方法发现,预测的分子更可能是抗生素,同时保持良好的类似药物样性能并易于合成。重要的是,我们的深度神经网络可以成功地过滤掉以综合分子,同时使用返回合成计划软件的$ 10^5美元$倍。

De novo molecule generation often results in chemically unfeasible molecules. A natural idea to mitigate this problem is to bias the search process towards more easily synthesizable molecules using a proxy for synthetic accessibility. However, using currently available proxies still results in highly unrealistic compounds. We investigate the feasibility of training deep graph neural networks to approximate the outputs of a retrosynthesis planning software, and their use to bias the search process. We evaluate our method on a benchmark involving searching for drug-like molecules with antibiotic properties. Compared to enumerating over five million existing molecules from the ZINC database, our approach finds molecules predicted to be more likely to be antibiotics while maintaining good drug-like properties and being easily synthesizable. Importantly, our deep neural network can successfully filter out hard to synthesize molecules while achieving a $10^5$ times speed-up over using the retrosynthesis planning software.

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