Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Grisoni, F; Reker, D; Schneider, P; Friedrich, L; Consonni, V; Todeschini, R; Koeberle, A; Werz, O; Schneider, G

Published Date

  • January 2017

Published In

Volume / Issue

  • 36 / 1-2

PubMed ID

  • 27650559

Electronic International Standard Serial Number (EISSN)

  • 1868-1751

International Standard Serial Number (ISSN)

  • 1868-1743

Digital Object Identifier (DOI)

  • 10.1002/minf.201600091


  • eng