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

2020/11/25 by Chenghao Liu, Liu, Cheng-Hao, Maksym Korablyov +9 · 1 citation
Biochemistry, Genetics and Molecular Biology · Computer Science · Materials Science · #Computational Drug Discovery Methods #FOS: Computer and information sciences #Machine Learning (cs.LG) #Machine Learning in Materials Science #Protein Structure and Dynamics

paper · pdf · doi:10.48550/arxiv.2011.13042

openalex publication_date 2020/11/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

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 105 times speed-up over using the retrosynthesis planning software.

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