Assessment of Binding Site and Development of Small Molecule Inhibitors
Targeting Epidermal Growth Factor Receptor Mutations in Non-Small
Cell Lung Cancer (NSCLC)

Kshipra   S.   Karnik; Aniket   P.   Sarkate; Aishwarya   P.   Rajhans; Pravin   S.   Wakte

doi:10.2174/1570180819666220523150059

Abstract

Background: Mutations occurring in the epidermal growth factor receptor of the tyrosine kinase family concerned with non-small cell lung cancer have been specifically targeted.

Objectives: The library design and R-group enhancement technique have been carried out on the preexisting marketed drugs to increase the binding affinity of the designed novel compounds. The screening of compounds was done using a flexible docking protocol.

Methods: Molecular docking studies provided information about binding pockets and interactions of molecules with the mutant (PDB: 4I1Z) as well as wild-type (PDB: 4I23) EGFR enzymes. The flexible docking was well supported by ADMET and molecular dynamic simulation studies.

Results: On the basis of docking score and protein-ligand interactions, the highest-scoring molecule was selected for molecular dynamics simulation, providing a complete insight into the ligand interaction and saturation.

Conclusion: The screened molecules can act as potential EGFR inhibitors in the management of drug resistance.

Keywords: Non-small cell lung cancer, EGFR, library design, virtual screening, molecular docking, molecular dynamics simulations.

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DOI https://dx.doi.org/10.2174/1570180819666220523150059	Print ISSN 1570-1808
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Assessment of Binding Site and Development of Small Molecule Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer (NSCLC)

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