Abstract
MEK proteins play a critical role in tumor proliferation, differentiation, and survival. Hence MEK1 inhibitors are of particular importance in the treatment of related diseases. The present study describes pharmacophore-based 3DQSAR model generation based on 82 known inhibitors of MEK1 allosteric binding cavity. The best pharmacophore model developed consisted of four features, namely AHHR. The model was used as a query to screen the databases of almost 1.3 million compounds. Finally, 8 hits were indentified and the docking study manifested that these compounds interacted with MEK1 well. Finally, 10 ns MD simulations of the obtained ligand-receptor system were performed. The stable binding mode of the system was determined. Our results showed that the identified 8 hits would be useful for the development of potent MEK1 agents.
Keywords: 3D-QSAR, Allosteric binding cavity, MD simulations, MEK1, Molecular docking, Virtual screening.
Letters in Drug Design & Discovery
Title:Identification of Potential MEK1 Inhibitors by Pharmacophore-based Virtual Screening and MD Simulations
Volume: 11 Issue: 7
Author(s): Huanhuan Shi, Lu Zhou, Guangkai Bao, Qianying Yi, Suwen Zhou, Yahui Tian and Xiaoli Li
Affiliation:
Keywords: 3D-QSAR, Allosteric binding cavity, MD simulations, MEK1, Molecular docking, Virtual screening.
Abstract: MEK proteins play a critical role in tumor proliferation, differentiation, and survival. Hence MEK1 inhibitors are of particular importance in the treatment of related diseases. The present study describes pharmacophore-based 3DQSAR model generation based on 82 known inhibitors of MEK1 allosteric binding cavity. The best pharmacophore model developed consisted of four features, namely AHHR. The model was used as a query to screen the databases of almost 1.3 million compounds. Finally, 8 hits were indentified and the docking study manifested that these compounds interacted with MEK1 well. Finally, 10 ns MD simulations of the obtained ligand-receptor system were performed. The stable binding mode of the system was determined. Our results showed that the identified 8 hits would be useful for the development of potent MEK1 agents.
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Cite this article as:
Shi Huanhuan, Zhou Lu, Bao Guangkai, Yi Qianying, Zhou Suwen, Tian Yahui and Li Xiaoli, Identification of Potential MEK1 Inhibitors by Pharmacophore-based Virtual Screening and MD Simulations, Letters in Drug Design & Discovery 2014; 11 (7) . https://dx.doi.org/10.2174/1570180811666140423221748
DOI https://dx.doi.org/10.2174/1570180811666140423221748 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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