Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening

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• 作者：Francesca Grisoni ; Daniel Reker ; Petra Schneider ; Lukas Friedrich ; Viviana Consonni ; Roberto Todeschini ; Andreas Koeberle ; Oliver Werz and Gisbert Schneider
• 刊名：Molecular Informatics
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：36
• 期：1-2
• 全文大小：1817K
• ISSN：1868-1751

文摘

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.