A collaborative constrained graph diffusion model for the generation of realistic synthetic molecules
On the map: Diffusion models → Flow matching, time series and science
Abstract (arXiv)
Developing new molecular compounds is crucial to address pressing challenges, from health to environmental sustainability. However, exploring the molecular space to discover new molecules is difficult due to the vastness of the space. Here we introduce CoCoGraph, a collaborative and constrained graph diffusion model capable of generating molecules that are guaranteed to be chemically valid. Thanks to the constraints built into the model and to the collaborative mechanism, CoCoGraph outperforms state-of-the-art approaches on standard benchmarks while requiring up to an order of magnitude fewer parameters. Analysis of 36 chemical properties also demonstrates that CoCoGraph generates molecules with distributions more closely matching real molecules than current models. Leveraging the model's efficiency, we created a database of 8.2M million synthetically generated molecules and conducted a Turing-like test with organic chemistry experts to further assess the plausibility of the generated molecules, and potential biases and limitations of CoCoGraph.
Key facts. No citing papers in the map yet (data through 14 Oct 2026). Placed in Flow matching, time series and science, one of 14 directions in Diffusion models. Builds on 30 of its 62 references that are in the map. First posted on arXiv 22 May 2025.
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30 of 62 references.
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- 2022Equivariant Diffusion for Molecule Generation in 3D31 Mar
- 2022Score-based Generative Modeling of Graphs via the System of Stochastic Differential Equations5 Feb
Other references · 22
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- 2022Diffusion Models: A Comprehensive Survey of Methods and Applicationscited by 1,114
- 2019Strategies for Pre-training Graph Neural Networkscited by 971
- 2018Junction Tree Variational Autoencoder for Molecular Graph Generationcited by 652
- 2020A Survey of Deep Active Learningcited by 554
- 2018GraphRNN: Generating Realistic Graphs with Deep Auto-regressive Modelscited by 413
- 2018MolGAN: An implicit generative model for small molecular graphscited by 393
10 more
- 2018GuacaMol: Benchmarking Models for De Novo Molecular Designcited by 297
- 2019Efficient Graph Generation with Graph Recurrent Attention Networkscited by 234
- 2022Exploring Chemical Space with Score-based Out-of-distribution Generationcited by 95
- 2022MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Designcited by 66
- 2020Scalable Deep Generative Modeling for Sparse Graphscited by 65
- 2023Diffusion Models for Constrained Domainscited by 63
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- 2023Conditional Diffusion Based on Discrete Graph Structures for Molecular Graph Generationcited by 46
- 2025DiffMS: Diffusion Generation of Molecules Conditioned on Mass Spectracited by 32
- 2023Metropolis Sampling for Constrained Diffusion Modelscited by 28
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