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Improving de novo molecular design with curriculum learning

Nature Machine Intelligence volume 4, pages 555–563 (2022)Cite this article

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An Author Correction to this article was published on 20 July 2022

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A preprint version of the article is available at ChemRxiv.

Abstract

Reinforcement learning is a powerful paradigm that has gained popularity across multiple domains. However, applying reinforcement learning may come at the cost of multiple interactions between the agent and the environment. This cost can be especially pronounced when the single feedback from the environment is slow or computationally expensive, causing extensive periods of non-productivity. Curriculum learning provides a suitable alternative by arranging a sequence of tasks of increasing complexity, with the aim of reducing the overall cost of learning. Here we demonstrate the application of curriculum learning for drug discovery. We implement curriculum learning in the de novo design platform REINVENT, and apply it to illustrative molecular design problems of different complexities. The results show both accelerated learning and a positive impact on the quality of the output when compared with standard policy-based reinforcement learning.

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Fig. 1: CL overview.
Fig. 2: CL target scaffold construction.
Fig. 3: Baseline RL versus CL to design PDK1 inhibitors.
Fig. 4: Baseline RL versus CL docking score distribution.
Fig. 5: Baseline RL versus CL unique Bemis–Murcko scaffolds.
Fig. 6: Agent knowledge retention and effects of curriculum objectives on the solution space diversity.

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Data availability

The trained generative model to reproduce the experiments in this work is provided at https://github.com/MolecularAI/ReinventCommunity/blob/master/notebooks/models/random.prior.new. The raw data that support the findings of this study are available from the corresponding author upon request.

Code availability

The code used in this study is available at https://github.com/MolecularAI/Reinvent. A corresponding tutorial for the code is available at https://github.com/MolecularAI/ReinventCommunity/blob/master/notebooks/Automated_Curriculum_Learning_Demo.ipynb. The specific frozen version of the code is available at https://zenodo.org/badge/latestdoi/486692494 (ref. 48). The DOI badge is provided at https://zenodo.org/badge/486692494.svg.

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Acknowledgements

We thank K. Giblin, A. Tomberg and E. Nittinger for constructive user feedback that helped us develop the concepts presented in work.

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Author notes

  1. These authors contributed equally: Jeff Guo, Vendy Fialková.

Authors and Affiliations

  1. Molecular AI, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden

    Jeff Guo, Vendy Fialková, Juan Diego Arango, Christian Margreitter, Kostas Papadopoulos, Ola Engkvist & Atanas Patronov

  2. Medicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

    Jon Paul Janet

  3. Department of Computer Science and Engineering, Chalmers University of Technology, Gothenburg, Sweden

    Ola Engkvist

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Contributions

V.F., J.G., J.D.A. and A.P. developed the code. J.G., A.P., J.P.J., C.M. and K.P. designed the experiments. J.G. performed the experiments and analyses. J.G. wrote the manuscript and all other authors revised it. A.P. supervised the work. All authors read and approved the final manuscript.

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Correspondence to Atanas Patronov.

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Nature Machine Intelligence thanks Christos Nicolaou and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Figs. 1–20, Discussion and Tables 1–4.

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Guo, J., Fialková, V., Arango, J.D. et al. Improving de novo molecular design with curriculum learning. Nat Mach Intell 4, 555–563 (2022). https://doi.org/10.1038/s42256-022-00494-4

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