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.
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