In drug design, the scaffold of a molecule is considered the main structure that determines its shape and places the functional moieties into the right positions to interact with the target. For this reason, developing new drug molecules with different cores but similar biological activities has been termed "scaffold hopping" . Combinatorial chemistry makes use of the concept in designing compound libraries by substituting a set of scaffolds with combinations of different side chains. And structures in chemical patents are often defined analogously as Markush structures . The intuitive chemical scaffold concept can also be utilised for classification purposes, especially in natural product (NP) research . In cheminformatics, scaffoldbased approaches can be applied for the analysis of high-throughput screening (HTS) data , mapping and visualising chemical spaces , or even train-test splits of molecular data sets for machine learning projects .