Flow matching for reaction pathway generation

Elucidating reaction mechanisms requires efficient generation of transition states (TSs) and products. Existing diffusion and sequence-based models accelerate parts of this process over traditional string-based methods, but typically still require manual enumeration of either TSs or products, and stochastic diffusion dynamics can be inefficient and hard to control. We introduce MolGEN, a conditional flow-matching framework that uses deterministic optimal transport to map Gaussian priors to chemical distributions. For TS generation, MolGEN improves TS geometry and barrier-height prediction over diffusion models while enabling sub-second sampling. For reaction product generation, it achieves competitive top-k accuracy while preserving mass and electron balance. Using the same backbone for TS and product sampling, MolGEN enables template-free generative exploration of reaction networks without the repeated quantum-chemistry searches required by prior methods. For the γ-ketohydroperoxide decomposition network, it produces more valid TSs than string-based methods using only 12 quantum-chemistry evaluations instead of 1156, and identifies a lower-barrier pathway.

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Publication Details

Journal
Nature Communications
Published
2026-07-17
DOI
https://doi.org/10.1038/s41467-026-75654-w
Primary Topic
Machine Learning in Materials Science
Type
article
Field-Weighted Citation Impact
0.00

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article

Flow matching for reaction pathway generation

Ping Tuo, Ju Li, Jiale Chen
Nature Communications
Machine Learning in Materials Science
article

Flow matching for reaction pathway generation

Ping Tuo, Ju Li, Jiale Chen
article en

Abstract

Elucidating reaction mechanisms requires efficient generation of transition states (TSs) and products. Existing diffusion and sequence-based models accelerate parts of this process over traditional string-based methods, but typically still require manual enumeration of either TSs or products, and stochastic diffusion dynamics can be inefficient and hard to control. We introduce MolGEN, a conditional flow-matching framework that uses deterministic optimal transport to map Gaussian priors to chemical distributions. For TS generation, MolGEN improves TS geometry and barrier-height prediction over diffusion models while enabling sub-second sampling. For reaction product generation, it achieves competitive top-k accuracy while preserving mass and electron balance. Using the same backbone for TS and product sampling, MolGEN enables template-free generative exploration of reaction networks without the repeated quantum-chemistry searches required by prior methods. For the γ-ketohydroperoxide decomposition network, it produces more valid TSs than string-based methods using only 12 quantum-chemistry evaluations instead of 1156, and identifies a lower-barrier pathway.

Nature Communications
Institute of Science and Technology Austria (AT), Massachusetts Institute of Technology (US), University of California, Berkeley (US)
U.S. Department of Energy, National Energy Research Scientific Computing Center
Openalex Percentile: Top 18%
Machine Learning in Materials Science
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