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