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Guided diffusion for inverse molecular design

Nature Computational Science volume 3, pages 873–882 (2023)Cite this article

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A preprint version of the article is available at ChemRxiv.

Abstract

The holy grail of materials science is de novo molecular design, meaning engineering molecules with desired characteristics. The introduction of generative deep learning has greatly advanced efforts in this direction, yet molecular discovery remains challenging and often inefficient. Herein we introduce GaUDI, a guided diffusion model for inverse molecular design that combines an equivariant graph neural net for property prediction and a generative diffusion model. We demonstrate GaUDI’s effectiveness in designing molecules for organic electronic applications by using single- and multiple-objective tasks applied to a generated dataset of 475,000 polycyclic aromatic systems. GaUDI shows improved conditional design, generating molecules with optimal properties and even going beyond the original distribution to suggest better molecules than those in the dataset. In addition to point-wise targets, GaUDI can also be guided toward open-ended targets (for example, a minimum or maximum) and in all cases achieves close to 100% validity of generated molecules.

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Fig. 1: Generation workflow.
Fig. 2: Guided generation of cc-PBH molecules to global minimum.
Fig. 3: Guided design of PASs with high HLG values.
Fig. 4: Guided design of narrow-band-gap molecules.

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Data availability

All data for cc-PBHs used in this project were obtained from the COMPAS project33, a freely available data repository at https://gitlab.com/porannegroup/compas. All PAS data are available free of charge at https://doi.org/10.5281/zenodo.7798697 (ref. 61). Source Data are provided with this paper.

Code availability

All codes used to train the models and generate molecules are provided free of charge at https://gitlab.com/porannegroup/gaudi (minted version https://doi.org/10.5281/zenodo.8311764)62. The repository also contains an original tutorial for generating GOR representations of PASs and for generating new PASs with user-defined target functions.

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Acknowledgements

We thank A. Wahab (ETH Zurich) for assistance with implementing the RDKit validity code and for proofreading the paper. We also thank A. Tsybizova (ETH Zurich) for proofreading and for providing helpful comments on the clarity of the text. We gratefully acknowledge P. Chen (ETH Zurich) for his scientific support and mentorship. E.M.Y., S.C. and R.G.P. are grateful for the financial support of the Branco Weiss Fellowship (awarded to R.G.P). R.G.P. is a Branco Weiss Fellow and a Horev Fellow. A.M.B. and T.W. were partially supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 863839) and by the Council For Higher Education - Planning & Budgeting Committee. L.C. is supported by the IRIDE grant from DAIS, Ca’ Foscari University of Venice.

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Authors and Affiliations

  1. Department of Computer Science, Technion—Israel Institute of Technology, Haifa, Israel

    Tomer Weiss & Alex M. Bronstein

  2. Schulich Faculty of Chemistry, Technion—Israel Institute of Technology, Haifa, Israel

    Eduardo Mayo Yanes, Sabyasachi Chakraborty & Renana Gershoni-Poranne

  3. University Ca’ Foscari of Venice, Venice, Italy

    Luca Cosmo

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Contributions

R.G.P. and A.M.B. conceived the original idea and designed and supervised the research project. T.W., L.C. and A.M.B. designed the generative and predictive models. T.W. wrote the code and trained the models. E.M.Y. and S.C. performed the quantum chemistry calculations. E.M.Y., S.C. and R.G.P. performed the dataset curation. T.W. and R.G.P. wrote the paper with the help of the other authors. The paper reflects the contributions of all authors.

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Correspondence to Alex M. Bronstein or Renana Gershoni-Poranne.

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Nature Computational Science thanks Ganna Gryn’ova, Rocío Mercado, Rostislav Fedorov and the other, anonymous reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Kaitlin McCardle, in collaboration with the Nature Computational Science team. Peer reviewer reports are available.

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Source data

Source Data Fig. 2

Numerical source data for data distribution.

Source Data Fig. 3

;Numerical source data for data distribution.

Source Data Fig. 4

Numerical source data for data distribution.

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Weiss, T., Mayo Yanes, E., Chakraborty, S. et al. Guided diffusion for inverse molecular design. Nat Comput Sci 3, 873–882 (2023). https://doi.org/10.1038/s43588-023-00532-0

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