Molecular docking study and molecular dynamics simulation of quinazoline derivatives targeting p53 and EGFR proteins as anti gastric cancer

Gastric cancer is closely associated with mutations in p53 and Epidermal Growth Factor Receptor (EGFR), disrupting key cellular regulatory functions.Quinazoline derivatives have demonstrated anticancer activity, yet their molecular interactions with p53 and EGFR remain unexplored.This study investigates these interactions through molecular docking, followed by structural optimization to enhance binding affinity.Stability was further assessed using molecular dynamics (MD) simulations, and pharmacokinetic properties were evaluated via ADMET analysis.The optimized derivatives Q-2, Q-4, and Q-9 showed strong binding affinities to p53 (Val147) with energies of -8.3120, -8.1330, and -8.1240 kcal/mol, and to EGFR (Asp831) with energies of -8.7090, -8.7800, and -9.1060 kcal/ mol.MD simulations revealed that Q-2-p53 and Q-9-EGFR complexes maintained high structural stability, while ADMET predictions confirmed favorable pharmacokinetics.These findings indicate that Q-2 and Q-9, as optimized forms of known quinazoline scaffolds, have strong potential as lead compounds for targeted gastric cancer therapy.