Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening.

TitleMatrix-based Molecular Descriptors for Prospective Virtual Compound Screening.
Publication TypeJournal Article
Year of Publication2017
AuthorsF Grisoni, D Reker, P Schneider, L Friedrich, V Consonni, R Todeschini, A Koeberle, O Werz, and G Schneider
JournalMolecular Informatics
Volume36
Issue1-2
Date Published01/2017
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.

DOI10.1002/minf.201600091
Short TitleMolecular Informatics