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Current Bioinformatics

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ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

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Research Article

Stability Analysis at Key Positions of EGFR Related to Non-small Cell Lung Cancer

Author(s): Avirup Ghosh* and Hong Yan

Volume 15, Issue 3, 2020

Page: [260 - 267] Pages: 8

DOI: 10.2174/1574893614666191212112026

Price: $65

Abstract

Background: Mutations in a protein called the Epidermal Growth Factor Receptor (EGFR) can cause Non-Small Cell Lung Cancer (NSCLC), which is the most common form of lung cancer. Many NSCLC cases arise from the L858R mutation, where Leucine (L) is replaced by arginine (R) at the 858th position in the EGFR, and that is also recognized as an exon 21 substitution. Moreover, half of the EKFR-mutated lung cancer patients develop acquired resistance to the first-generation EGFR-TKIs due to another mutation T790M.

Objective: In this research work, a novel method is used to investigate the possible reason for the EGFR mutation to takes place in the specific 858th and 790th position, and also, we evaluated the hydrogen bonds to measure the overall stability of different structures.

Methods: We performed the molecular dynamics simulation and used Amber tool to achieve our primary objectives and later we use CPPTRAJ to analyze other changes in the hydrogen bonds for different mutational structures of EGFR.

Results: First, we investigated the hydrogen bonds in different positions in the EGFR kinase domain and estimated why the first stage mutation (L858R) and resistance mutation (L858R/T790M) take place in the 858th and 790th position respectively. We found the hydrogen bond counts in the 858th and 790th position is lesser than the neighborhood positions and that yields to achieve a least stability in that position.

Conclusion: Our method represents an important contribution to molecular dynamics analysis for NSCLC studies. The results obtained from this study provide a useful insight into the NSCLC drug resistance.

Keywords: EGFR, Non-Small Cell Lung Cancer (NSCLC), gene mutation, stability analysis, molecular dynamics analysis, kinase.

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