FragFlex: Fragment-Based Flexible Molecular Generation for Exploring Vast Chemical Space

arXiv:2610.15284v1 Announce Type: new Abstract: Drug discovery requires efficient exploration of an astronomically large chemical space. Molecular graph diffusion models offer a promising approach to this task, but many require graph size to be fixed before generation. Although atom-level insertion and deletion can enable flexible-size generation, jointly modeling molecular size, atom types, and bonds while maintaining chemical validity remains challenging. We introduce FragFlex, a flexible-length discrete diffusion model that performs node insertion and deletion at the fragment level. During denoising, FragFlex jointly learns the size, fragment identities, and inter-fragment connectivity of the fragment graph. A neural attachment-site predictor and valence-aware assembler then convert the generated fragment graph into an atom-level molecule. In large-scale experiments generating 10 million molecules, FragFlex achieves near-perfect chemical validity while maintaining high uniqueness, demonstrating a strong balance between the two.

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Source: arXiv cs.LG | 2026-10-14