Molecular docking, MM/GBSA and 3D-QSAR studies on EGFR inhibitors

Journal of Chemical Sciences

RAJU BATHINI¹  VIJJULATHA MANGA¹  SABIHA FATIMA¹  SREE KANTH SIVAN¹ 

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关键词: Epidermal growth factor receptor (EGFR);    Extra precision (XP) docking;    3D-QSAR;    Comparative molecular field analysis (CoMFA);    Comparative molecular similarity indices analysis (CoMSIA);    Molecular mechanics;    generalized born surface area (GBSA).;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Epidermal growth factor receptor (EGFR) is the first growth factor receptor proposed as a target for cancer therapy. Molecular modeling protocols like molecular docking, molecular mechanics/generalized born surface area (MM/GBSA) calculations and three dimensional-quantitative structure activity relationship(3D-QSAR) studies were performed on 45 molecules to understand the structural requirements for EGFR tyrosine kinase inhibitors. Conformation for all the molecules obtained from molecular docking were used as is for 3D-QSAR analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarityindices analysis (CoMSIA) models were obtained by performing partial least square analysis on 35 training molecules and these models were validated using 10 test moleucles. The models showed good statistical results in terms of r², q²loo and r² pred values. Information rendered from 3D-QSAR model and sitemap analysis was used to optimize lead molecule to design prospective inhibitors. Improvement in EGFR binding affinity can be achieved by substitutional modification on phenyl ring attached to alkynyl group with bulkier hydrogen bond donor and acceptor substituents that can increase favourable interaction with the receptor.

【 授权许可】

Unknown