De Novo Drug Design by Iterative Multi-Objective Deep Reinforcement Learning with Graph-based Molecular Quality Assessment.

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Abstract

Generating molecules of high quality and drug-likeness in the vast chemical space is a big challenge in the drug discovery. Most existing molecule generative methods focus on diversity and novelty of molecules, but ignoring drug potentials of the generated molecules during the generation process.In this study, we present a novel de novo multi-objective quality assessment-based drug design approach QADD, which integrates an iterative refinement framework with a novel graph-based molecular quality assessment model on drug potentials. QADD designs a multi-objective deep reinforcement learning pipeline to generate molecules with multiple desired properties iteratively, where a graph neural network-based model for accurate molecular quality assessment on drug potentials is introduced to guide molecule generation. Experimental results show that QADD can jointly optimize multiple molecular properties with a promising performance and the quality assessment module is capable of guiding the generated molecules with high drug potentials. Furthermore, applying QADD to generate novel molecules binding to a biological target protein DRD2 also demonstrates the algorithm’s efficacy.QADD is freely available online for academic use at https://github.com/yifang000/QADD or http://www.csbio.sjtu.edu.cn/bioinf/QADD.Supplementary data are available at Bioinformatics online.© The Author(s) 2023. Published by Oxford University Press.