Fast Substructure Search in Combinatorial Library Spaces

17 February 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


We present an efficient algorithm for substructure search in combinatorial libraries defined by synthons, i.e. substructures with connection points. Our method improves on existing approaches by introducing powerful heuristics and fast fingerprint screening to quickly eliminate branches of non matching combinations of synthons. With this we achieve typical response times of a few seconds on a standard desktop computer for searches in large combinatorial libraries like the Enamine REAL space. We published the Java source as part of the OpenChemLib under the BSD license, and we implemented tools to enable substructure search in custom combinatorial libraries.


substructure search
combinatorial libraries
combinatorial library spaces
fingerprint filtering
virtual screening
synthon spaces
medicinal chemistry

Supplementary materials

FFP Fragment IDCodes
OpenChemLib IDCodes of the substructure fragments of the fragment fingerprint.
Benchmark Results for Search in Enamine REAL Space
Benchmark results of 3000 small molecule queries in the Enamine REAL Space

Supplementary weblinks


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