title: A novel multi-target drug screening strategy directed against key proteins of DAPk family.
abstract: Screening and identifying multi-target ligands becomes a daunting task when there are very few matching pharmacophoric features among the proteins. Herein, we describe a novel screening strategy to identify multi-target ligands for proteins having varying pharmacophoric features with their ligands. This strategy was adopted to identify multi-target ligands for death-associated protein kinase (DAPk) family. The role of the kinase activity of DAPk in eukaryotic cell apoptosis and the ability of bioavailable DAPk inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for neurodegenerative disorders. In this work, we employed a novel strategy using the existing computational approaches to design multi-target inhibitors, which can potentially inhibit one or any combination of the three DAPk family members. The strategy employs a combination of merged pharmacophore matching, database screening and molecular docking to reliably identify potential multi-target inhibitors targeted against DAPk protein family.
authors.affiliation: School of Biotechnology, Coordinator, DBT-Bioinformatics Centre, National Institute of Technology Calicut, Calicut 673601, India.
authors.forename: Syam B
authors.initials: SB
authors.lastname: Nair
authors.forename: Shaik M
authors.initials: SM
authors.lastname: Fayaz
authors.forename: Golgodu K
authors.initials: GK
authors.lastname: Rajanikant
mesh_terms: D001665:Binding Sites; D016923:Cell Death; D064550:Death-Associated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D064550:Death-Associated Protein Kinases