Identification of Bioactive Scaffolds Based on QSAR Models
Tomoki Nakagawa, Tomoyuki Miyao, Kimito Funatsu · Molecular Informatics · 2017
In medicinal chemistry, the molecular scaffolds commonly found in compounds with preferable biological activities are called bioactive scaffolds. They are important because if present in a structure, it is more likely that the compound will be bioactive. Traditionally, medicinal chemists use their knowledge to identify bioactive scaffolds from a given data set after systematic extraction of all candidate scaffolds. However, manually sorting all the scaffolds is not practical as the number of compounds in a data set is often very large. Herein, we propose a method to systematically identify bioactive scaffolds based on a structure generator and a QSAR model. Two proof-of-concept studies showed that known bioactive scaffolds as well as scaffolds containing important substructures were extracted. The proposed method does not depend on scaffold frequencies in a data set, which is different from currently used methods for bioactive scaffold identification.