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BioMed Research International
Volume 2014 (2014), Article ID 139492, 9 pages
http://dx.doi.org/10.1155/2014/139492
Research Article

In Silico Investigation of Potential mTOR Inhibitors from Traditional Chinese Medicine for Treatment of Leigh Syndrome

1School of Pharmacy, China Medical University, Taichung 40402, Taiwan
2School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan
3Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan
4 Department of Neurosurgery, China Medical University Hospital, Taichung 40447, Taiwan
5Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
6Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan

Received 23 February 2014; Revised 5 March 2014; Accepted 5 March 2014; Published 23 June 2014

Academic Editor: Chung Y. Hsu

Copyright © 2014 Kuan-Chung Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A recent research demonstrates that the inhibition of mammalian target of rapamycin (mTOR) improves survival and health for patients with Leigh syndrome. mTOR proteins can be treated as drug target proteins against Leigh syndrome and other mitochondrial disorders. In this study, we aim to identify potent TCM compounds from the TCM Database@Taiwan as lead compounds of mTOR inhibitors. PONDR-Fit protocol was employed to predict the disordered disposition in mTOR protein before virtual screening. After virtual screening, the MD simulation was employed to validate the stability of interactions between each ligand and mTOR protein in the docking poses from docking simulation. The top TCM compounds, picrasidine M and acerosin, have higher binding affinities with target protein in docking simulation than control. There have H-bonds with residues Val2240 and π interactions with common residue Trp2239. After MD simulation, the top TCM compounds maintain similar docking poses under dynamic conditions. The top two TCM compounds, picrasidine M and acerosin, were extracted from Picrasma quassioides (D. Don) Benn. and Vitex negundo L. Hence, we propose the TCM compounds, picrasidine M and acerosin, as potential candidates as lead compounds for further study in drug development process with the mTOR protein against Leigh syndrome and other mitochondrial disorders.