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BioMed Research International
Volume 2014, Article ID 189495, 14 pages
http://dx.doi.org/10.1155/2014/189495
Research Article

In Silico Investigation of Potential Pyruvate Kinase M2 Regulators from Traditional Chinese Medicine against Cancers

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
4Department of Anesthesiology, 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 22 February 2014; Revised 5 March 2014; Accepted 5 March 2014; Published 25 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 in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted from Lycium chinense Mill. and Abrus precatorius L., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.