In silico analysis of the effect of mutation on epidermal growth factor receptor in non-small-cell lung carcinoma: from mutational analysis to drug designing

Journal of Biomolecular Structure & Dynamics
Fu-Li ZhaoChen Zeng

Abstract

Tyrosine kinase inhibitors (TKI)-resistant mutation in epidermal growth factor receptor's (EGFR) kinase domain is an important anomaly to look into. Studying the mutations at atomic level using molecular dynamics simulations gave us an insight into the architectural changes happening at the microscopic level. The knowledge was used to design new TKI whose function is devoid of the affect of the mutations in kinase domain. Traditional Chinese medicinal library was used for structure-based drug designing, where virtual screening was followed by ADME/Tox analysis and the shortlisted compounds were docked into the kinase domain of EGFR and simulated there using atomic-level selection of the grid. The shortlisted compounds from molecular docking analysis were subjected to MM-PBSA calculations. The in silico data generated is giving a strong lead compound for further in vitro and in vivo analysis.

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Citations

May 27, 2016·Journal of Biomolecular Structure & Dynamics·Yan QiaoJunbiao Chang
Oct 4, 2016·Journal of Biomolecular Structure & Dynamics·Alireza FarasatAmir Homayoun Keihan
Apr 28, 2017·Journal of Biomolecular Structure & Dynamics·Nurbubu T MoldogazievaAlexander A Terentiev
Jun 11, 2017·Journal of Biomolecular Structure & Dynamics·Libo YanHaoliang Yuan
Jan 26, 2018·Frontiers in Molecular Biosciences·Changhao WangRay Luo
Feb 24, 2018·Journal of Biomolecular Structure & Dynamics·Jiajie XiaoFreddie R Salsbury

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Methods Mentioned

BETA
X-ray
MDS

Software Mentioned

Discovery Studio
SASA
Autodock
do
XMGRACE
sas
GROMOS
MDS
PRODRG
PBSA

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