VFMol: A Discrete Flow Matching Variational Autoencoder for Molecular Graph Generation

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Authors: Yanglan Gan, Jieli Su, Kaili Wang, Guangwei Xu, Guobing Zou
Cited by: 1
References: 17

Abstract

Molecular graph generation is a key task in drug discovery, aiming to efficiently identify novel compounds with desired properties. While variational autoencoders (VAEs) excel at latent space modeling and discrete flow matching (DFM) enables efficient continuous-time sampling, existing approaches still face critical limitations. VAE decoders struggle with permutation invariance and suffer from one-shot generation bottlenecks, whereas DFM models often rely on a fixed prior initialization that lacks adaptability to specific molecular structures. To address these issues, we propose VFMol, a novel framework that synergistically integrates personalized VAE latent space modeling with the efficient stepwise sampling mechanism of DFM in the discrete space. Specifically, the encoder learns a posterior distribution tailored to each input graph as the generation starting point, thereby enhancing both structural fidelity and diversity. Moreover, we introduce a lightweight property-guided framework based on KAN and classifier-free guidance, enabling conditional generation without auxiliary property predictors. Experiments on two widely used molecular data sets demonstrate that VFMol achieves state-of-the-art performance in terms of molecular structural quality and property controllability, verifying its generality and effectiveness.

Fields of Study & Subjects

Advanced Graph Neural Networks Graph Theory and Algorithms Computational Drug Discovery Methods

Publication details

Journal / source
Journal of Chemical Information and Modeling
Publisher
American Chemical Society (ACS)
Volume
66
Issue
6
Pages
3320–3330
Publication date
26 February 2026
Language
EN