title: In silico deconstruction of ATP-competitive inhibitors of glycogen synthase kinase-3β.
abstract: Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical expansion. For instance, the question of the binding conservation upon fragmentation of a molecule is still unclear. A number of papers have challenged this hypothesis by means of experimental techniques, with controversial results, "underlining" the idea that a simple generalization, maybe, is not possible. From a computational standpoint, the issue has been rarely addressed and mostly to test novel protocols on limited data sets. To fill this gap, we here report on a computational retrospective study concerned with the in silico deconstruction of leadlike compounds, active on the pharmaceutically relevant enzyme glycogen synthase kinase-3β.
authors.affiliation: Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bisignano
authors.forename: Chiara
authors.initials: C
authors.lastname: Lambruschini
authors.forename: Manuele
authors.initials: M
authors.lastname: Bicego
authors.forename: Vittorio
authors.initials: V
authors.lastname: Murino
authors.forename: Angelo D
authors.initials: AD
authors.lastname: Favia
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001667:Binding, Competitive; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
chemical_list: D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3