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A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
Institute of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
Institute of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China
Fujian Supercomputer Center, Fuzhou, Fujian 350108, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 6 March 2011; in revised form: 19 July 2011 / Accepted: 22 July 2011 / Published: 15 August 2011
Abstract: The main functional components of green tea, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), are found to have a broad antineoplastic activity. The discovery of their targets plays an important role in revealing the antineoplastic mechanism. Therefore, to identify potential target proteins for tea polyphenols, we have taken a comparative virtual screening approach using two reverse docking systems, one based on Autodock software and the other on Tarfisdock. Two separate in silico workflows were implemented to derive a set of target proteins related to human diseases and ranked by the binding energy score. Several conventional clinically important proteins with anti-tumor effects are screened out from the PDTD protein database as the potential receptors by both procedures. To further analyze the validity of docking results, we study the binding mode of EGCG and the potential target protein Leukotriene A4 hydrolase in detail. We indicate that interactions mediated by electrostatic and hydrogen bond play a key role in ligand binding. EGCG binds to the enzyme with certain orientation and conformation that is suitable for nucleophilic attacks by several electrical residues inside the enzyme’s activity cavity. This study provides useful information for studying the antitumor mechanism of tea’s functional components. The comparative reverse docking strategy presented generates a tractable set of antineoplastic proteins for future experimental validation as drug targets against tumors.
Keywords: tea polyphenols; reverse docking; target protein; binding mode; virtual screening
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Zheng, R.; Chen, T.-S.; Lu, T. A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode. Int. J. Mol. Sci. 2011, 12, 5200-5212.
Zheng R, Chen T-S, Lu T. A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode. International Journal of Molecular Sciences. 2011; 12(8):5200-5212.
Zheng, Rong; Chen, Tuan-sheng; Lu, Tun. 2011. "A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode." Int. J. Mol. Sci. 12, no. 8: 5200-5212.