title: Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery.
abstract: Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.
authors.affiliation: Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest 1117, Hungary.
authors.forename: David
authors.initials: D
authors.lastname: Bajusz
authors.affiliation: Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest 1117, Hungary.
authors.forename: Gyorgy G
authors.initials: GG
authors.lastname: Ferenczy
authors.affiliation: Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest 1117, Hungary.
authors.forename: Gyorgy M
authors.initials: GM
authors.lastname: Keseru
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
keywords: Activation segment; Covalent docking; DFG motif; Docking; Drug discovery; Inhibitor; Kinase; Structure-based virtual screening; hinge