Abstract
Molecular descriptors capture diverse structural information of molecules and are a prerequisite for ligand-based similarity searching. In this study, we introduce topological matrix-based descriptors to virtual screening for hit discovery. We evaluated the usefulness of matrix-based descriptors in a retrospective setting and compared them with topological pharmacophore descriptors. Special attention was given to the influence of data pre-processing and the applied similarity metric on the virtual screening performance. Overall, the MB descriptors showed a competitive and complementary performance to other descriptors. A prospective screen of a commercial compound library led to the discovery of a novel natural-product-derived cyclooxygenase-2 inhibitor predicted to interact differently with the target protein compared to the query compound ibuprofen. The results of our study motivate the use of matrix-based descriptors for molecular similarity-based virtual screening and scaffold hopping.
Original language | English |
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Article number | 1600091 |
Journal | Molecular Informatics |
Volume | 36 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords
- cheminformatics
- cyclooxygenase
- drug discovery
- molecular similarity
- natural product