VIJJULATHA MANGA
Articles written in Journal of Chemical Sciences
Volume 128 Issue 7 July 2016 pp 1163-1173 Regular Article
Molecular docking, MM/GBSA and 3D-QSAR studies on EGFR inhibitors
RAJU BATHINI SREE KANTH SIVAN SABIHA FATIMA VIJJULATHA MANGA
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, q²
loo 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.
Volume 134, 2022
All articles
Continuous Article Publishing mode
Click here for Editorial Note on CAP Mode
© 2021-2022 Indian Academy of Sciences, Bengaluru.