STAMP as a topology-aware molecular language for fragment-level learning and editing

Abstract:Molecular fragments provide chemically meaningful units, but existing molecular languages rarely make their locations and connections explicit for editing. Here we introduce STAMP (Sequential Tree Attachment-based Motif-Preserving representation), a topology-aware molecular language that connects fragment-level representation learning with precise structural editing. STAMP separately encodes motif identity, attachment sites and tree topology, making fragments reusable across contexts and subtrees directly accessible. Learned representations capture motif similarity and recurring transformations, and lower activity-cliff prediction error on 23 of 30 targets versus a matched SMILES encoder. Compatible subtree operations support scaffold-preserving optimization, ranking first among six methods on 15 of 23 benchmark objectives. A deterministic compiler enables frozen language models to act on indexed fragments, improving molecular editing, optimization, transformation transfer and change identification by 9 to 56 percentage points over plain SMILES. Together, these results establish an executable molecular language in which learned chemical units remain directly operable during design.

Quantitative Methods (q-bio.QM); Artificial Intelligence (cs.AI)

arXiv:2610.18438 [q-bio.QM]

(or arXiv:2610.18438v1 [q-bio.QM] for this version)

https://doi.org/10.48550/arXiv.2610.18438 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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