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A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode

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 mech...

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Detalles Bibliográficos
Autores principales: Zheng, Rong, Chen, Tuan-sheng, Lu, Tun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179160/
https://www.ncbi.nlm.nih.gov/pubmed/21954353
http://dx.doi.org/10.3390/ijms12085200
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author Zheng, Rong
Chen, Tuan-sheng
Lu, Tun
author_facet Zheng, Rong
Chen, Tuan-sheng
Lu, Tun
author_sort Zheng, Rong
collection PubMed
description 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.
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spelling pubmed-31791602011-09-27 A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode Zheng, Rong Chen, Tuan-sheng Lu, Tun Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2011-08-15 /pmc/articles/PMC3179160/ /pubmed/21954353 http://dx.doi.org/10.3390/ijms12085200 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zheng, Rong
Chen, Tuan-sheng
Lu, Tun
A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title_full A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title_fullStr A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title_full_unstemmed A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title_short A Comparative Reverse Docking Strategy to Identify Potential Antineoplastic Targets of Tea Functional Components and Binding Mode
title_sort comparative reverse docking strategy to identify potential antineoplastic targets of tea functional components and binding mode
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179160/
https://www.ncbi.nlm.nih.gov/pubmed/21954353
http://dx.doi.org/10.3390/ijms12085200
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