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

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 pre-existing 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.