At Idorsia we see a dramatic impact on drug discovery in multiple ways. Search in commercial combinatorial libraries using this method became a key technology for drug discovery and is used on a daily basis through all phases of drug discovery projects. The configurable Figure : Summary of the results of the benchmark based on the 2997 considered structures from DrugCentral. Please note that results are not for the specific structure, but for the substructure including all superstructures of the query. We considered queries with in between 12 and 32 atoms, and we excluded molecules containing decyl groups (i.e. very long alkylic chains). (A) Overview of query times. (B) Plot of query times versus the number of enumerated hits (without checking for uniqueness of the assembled structures, only based on matching synthons). ffp bits is the number of set bits in the fragment fingerprint. Please note that this plot only includes queries that returned hits. (C) Plot of query times versus set bits in the fragment fingerprint including some example structures. The color indicates whether the query returned hits. substructure queries provided by the OpenChemLib allow us, to search for very specific classes of structures, e.g. for replacing specific parts of molecules or for scaffold hopping. This if often used in automated workflows that integrate modeling and prediction of properties. Following up the advent of this technology, we are currently in the process of largely automating the first phases of small molecule drug discovery projects.