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Int. J. Mol. Sci. 2016, 17(3), 340;

Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases

College of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin, China
State Key Laboratory of MicrobialMetabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130000, Jilin, China
Author to whom correspondence should be addressed.
Academic Editor: Christo Z. Christov
Received: 3 February 2016 / Revised: 27 February 2016 / Accepted: 1 March 2016 / Published: 4 March 2016
PDF [2176 KB, uploaded 4 March 2016]


Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery. View Full-Text
Keywords: pyruvate dehydrogenase kinase; inhibitor; virtual screening; coumarins pyruvate dehydrogenase kinase; inhibitor; virtual screening; coumarins

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Zhou, X.; Yu, S.; Su, J.; Sun, L. Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases. Int. J. Mol. Sci. 2016, 17, 340.

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