Flow matching for reaction pathway generation

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Authors: Ping Tuo, Jiale Chen, Ju Li
Cited by: 1
References: 48

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.

Fields of Study & Subjects

Machine Learning in Materials Science Computational Drug Discovery Methods Protein Structure and Dynamics

Publication details

Journal / source
Nature Communications
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Publication date
17 July 2026
Language
EN