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

• DOI: 10.3390/ijms12085200
• Publication Date: 2011-08-15T14:36:49Z
• Authors: Rong Zheng; Tuan-sheng Chen; Tun Lu
• Keywords: Epoxide Hydrolases; Models, Molecular; 0303 health sciences; Tea; Molecular Conformation; Polyphenols; Quantitative Structure-Activity Relationship; Antineoplastic Agents; Article; Catechin; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Drug Discovery; Humans; Computer Simulation; tea polyphenols; reverse docking; target protein; binding mode; virtual screening; Protein Binding

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.