Insights from molecular modeling, docking and simulation of imidazole nucleus containing chalcones with EGFR kinase domain for improved binding function

EGFR Kinase domain is a crucial role player cell surface receptor protein activated by specific binding of its ligand like EGFR. Importance of this protein as a therapeutically important drug target towards treating various cancer types has been proven elsewhere in previous literature. In this present study, we have designed a novel series of five compounds and computationally evaluated their potential to act as inhibitors of EGFR kinase domain towards anti-cancer activity. Our docking study shows compounds have the potential to dock into the active site of the EGFR Kinase domain with a binding energy in a range of -5.46 to - 7.32 Kcal/mol, Among all the compounds, compound 2 was found to be the lead like molecule with the binding energy of -7.32 kcal/mol with predicted IC50 value of 4.33 micro molar level. Molecular dynamic simulation studies for this compound 2 in complex with EGFR kinase domain has revealed several interesting molecular interactions with some of the important residues present at the active binding site of EGFR Kinase domain. Conclusively, novel designed compound 2 of the present study have shown promising anti-cancer potential worth considering for further evaluations.