Abstract
Protein kinases are among the most exploited targets in modern drug discovery due to key roles these enzymes play in human diseases including cancer. The in silico approach, an important part of rational design of protein kinase inhibitors, is founded on vast information about 3D structures of these enzymes. This review summarizes general structural features of the kinase inhibitors and the studies applied toward a large scale chemical database for virtual screening. Analyzed are the ways of validating the modern docking tools and their combinations with different scoring functions. In particular, we discuss the kinase flexibility as a reason for failures of the docking procedure. Finally, evidence is provided for the main patterns of kinase-inhibitor interactions and creation of the hinge-region-directed 2D filters.
Keywords: Protein kinase inhibitors, in silico analysis, receptor based approach, docking, scoring
Anti-Cancer Agents in Medicinal Chemistry
Title: In Silico Design of Protein Kinase Inhibitors: Successes and Failures
Volume: 7 Issue: 2
Author(s): Galina G. Dubinina, Oleksandr O. Chupryna, Maxim O. Platonov, Petro O. Borisko, Galina V. Ostrovska, Andriy O. Tolmachov and Alexander A. Shtil
Affiliation:
Keywords: Protein kinase inhibitors, in silico analysis, receptor based approach, docking, scoring
Abstract: Protein kinases are among the most exploited targets in modern drug discovery due to key roles these enzymes play in human diseases including cancer. The in silico approach, an important part of rational design of protein kinase inhibitors, is founded on vast information about 3D structures of these enzymes. This review summarizes general structural features of the kinase inhibitors and the studies applied toward a large scale chemical database for virtual screening. Analyzed are the ways of validating the modern docking tools and their combinations with different scoring functions. In particular, we discuss the kinase flexibility as a reason for failures of the docking procedure. Finally, evidence is provided for the main patterns of kinase-inhibitor interactions and creation of the hinge-region-directed 2D filters.
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Cite this article as:
Dubinina G. Galina, Chupryna O. Oleksandr, Platonov O. Maxim, Borisko O. Petro, Ostrovska V. Galina, Tolmachov O. Andriy and Shtil A. Alexander, In Silico Design of Protein Kinase Inhibitors: Successes and Failures, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (2) . https://dx.doi.org/10.2174/187152007780058704
DOI https://dx.doi.org/10.2174/187152007780058704 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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