title: Scoring of de novo Designed Chemical Entities by Macromolecular Target Prediction.
abstract: Computational de novo molecular design and macromolecular target prediction have become routine in applied cheminformatics. In this study, we have generated populations of drug template-derived designs using ligand-based building block assembly, and predicted their potential targets. The results of our analysis show that the reaction-based de novo design generated new chemical entities with similar properties and pharmacophores as that of the template drugs as well as up to 44 % of the de novo compounds receiving the correct target predictions. Keeping in mind the probabilistic nature of the methods, such a combination of fast and meaningful computational structure generation by reaction-based design and product scoring by target class prediction may be appropriate for prospective application in medicinal chemistry.
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-, 8093, Zurich, Switzerland.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Button
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-, 8093, Zurich, Switzerland.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-, 8093, Zurich, Switzerland.|inSili.com LLC, Segantinisteig 3, CH-, 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, CH-, 8093, Zurich, Switzerland.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D015195:Drug Design; D062105:Molecular Docking Simulation / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries
keywords: Cheminformatics; drug design; medicinal chemistry; polypharmacology; structure-activity relationship