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.

Grisoni, F., Reker, D., Schneider, P., Friedrich, L., Consonni, V., Todeschini, R., et al. (2017). Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening. MOLECULAR INFORMATICS, 36(1-2, Special Issue) [10.1002/minf.201600091].

Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening

GRISONI, FRANCESCA
Primo
;
CONSONNI, VIVIANA;TODESCHINI, ROBERTO;
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.
Articolo in rivista - Articolo scientifico
cheminformatics; cyclooxygenase; drug discovery; molecular similarity; natural product
English
2017
36
1-2, Special Issue
1600091
none
Grisoni, F., Reker, D., Schneider, P., Friedrich, L., Consonni, V., Todeschini, R., et al. (2017). Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening. MOLECULAR INFORMATICS, 36(1-2, Special Issue) [10.1002/minf.201600091].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/152436
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