title: Matrix-based Molecular Descriptors for Prospective Virtual Compound Screening.
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.
authors.affiliation: University of Milano-Bicocca, Dept. of Earth and Environmental Sciences, P.za della Scienza 1, 20126, Milano, Italy.|Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grisoni
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Reker
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.|inSili.com LLC, Segantinisteig 3, 8049, Zurich, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Friedrich
authors.affiliation: University of Milano-Bicocca, Dept. of Earth and Environmental Sciences, P.za della Scienza 1, 20126, Milano, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Consonni
authors.affiliation: University of Milano-Bicocca, Dept. of Earth and Environmental Sciences, P.za della Scienza 1, 20126, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Todeschini
authors.affiliation: University of Jena, Institute of Pharmacy, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koeberle
authors.affiliation: University of Jena, Institute of Pharmacy, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D001665:Binding Sites; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D054852:Small Molecule Libraries; D051546:Cyclooxygenase 2
keywords: cheminformatics; cyclooxygenase; drug discovery; molecular similarity; natural product