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Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery

[ Vol. 17 , Issue. 20 ]

Author(s):

David Bajusz, Gyorgy G. Ferenczy and Gyorgy M. Keseru*   Pages 2235 - 2259 ( 25 )

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.

Keywords:

Drug discovery, Kinase, Structure-based virtual screening, Inhibitor, Docking, DFG motif, Activation segment, hinge, Covalent docking.

Affiliation:

Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest 1117, Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest 1117, Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok korutja 2, Budapest 1117

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