Comparison of Combinatorial Fragment Spaces and Its Application to Ultralarge Make-on-Demand Compound Catalogs

The set of chemical
compounds shared by two or more chemical libraries
is assessed routinely as means of comparing these libraries for various
applications. Traditionally this is achieved by comparing the members
of the chemical libraries individually for identity. This approach
becomes impractical when operating on chemical libraries exceeding
billions or even trillions of compounds in size. As a result, no such
analysis exists for ultralarge chemical spaces like the Enamine REAL
Space containing over 20 billion compounds. In this work, we present
a novel tool called SpaceCompare for the overlap calculation of large,
nonenumerable combinatorial fragment spaces. In contrast to existing
methods, SpaceCompare utilizes topological fingerprints and the combinatorial
character of these chemical spaces. The tool is able to determine
the exact overlap of prominent spaces like Enamine’s REAL Space,
WuXi’s GalaXi Space, and Otava’s CHEMriya for the first
time.