Magic Rings: Navigation in the Ring Chemical Space Guided by the Bioactive Rings

Rings and scaffolds are likely the most important part of bioactive molecules since they define the shape of the ligand and orient the substituents into the right positions for interactions with the target. 98% of compounds from the ChEMBL database contain at least one ring system. Peter Ertl used this as a motivation for his study to identify those and analyze them for their frequency and target structures. Using a set of 42 simple topological descriptors, data from the ChEMBL and ZINC database was analyzed revealing minor differences between the distribution of bioactive and common synthetic rings. For bioactive systems fused aromatic rings often containing a nitrogen were reported, while synthetic systems on the other hand featured aliphatic rings and spiro centers. The bioactive rings were classified into eight different categories depending on their preferred target: GPCRs, kinases, proteases, other enzymes, nuclear receptors, ion channels, epigenetic, multiple, and other, totaling in fourty thousand individual rings. An interactive, visual map was designed, capturing the size and complexity of the investigated ring systems. Clusters of bioactive regions within the chemical space were observed.
The data set can further be used for various approaches including diversification of molecule collections, virtual screenings, library designs, and many more. A ReCore index of the bioactive ring systems featuring 15 million entries with two exit vectors each is available for SeeSAR.
BioSolveIT DrugSpace 2022 "It's a small world"
Speaker: Peter Ertl (Novartis)
Website: peter-ertl.com/
Publication: pubs.acs.org/doi/10.1021/acs....
ReCore index for SeeSAR: www.biosolveit.de/SeeSAR#frag...