Letters in Drug Design & Discovery

Atta-ur-Rahman  , FRS
Honorary Life Fellow
Kings College
University of Cambridge
Email: lddd@benthamscience.org


Identification of Potential MEK1 Inhibitors by Pharmacophore-based Virtual Screening and MD Simulations

Author(s): Huanhuan Shi, Lu Zhou, Guangkai Bao, Qianying Yi, Suwen Zhou, Yahui Tian and Xiaoli Li

Affiliation: College of Chemical Engineering, Sichuan University, Sichuan, Chengdu, 610065, China.

Graphical 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.

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Page: [894 - 907]
Pages: 14
DOI: 10.2174/1570180811666140423221748