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

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

Volume: 17 Issue: 20

Author(s): David Bajusz, Gyorgy G. Ferenczy and Gyorgy M. Keseru*

Affiliation:

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

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

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.

Cite this article as:

Bajusz David, Ferenczy G. Gyorgy and Keseru M. Gyorgy*, Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery, Current Topics in Medicinal Chemistry 2017; 17 (20) . https://dx.doi.org/10.2174/1568026617666170224121313