A series of novel 4-anilino quinazoline derivatives were taken based on the literature study and optimized with Autodock version 4.2 and molecular dynamics (MD) protocol to investigate the interaction between the target compounds and the amino acid residues of target protein epidermal growth factor receptor (EGFR) tyrosine kinase (PDB ID: 1M17). The free energies of binding and inhibition constants (Ki) of the docked ligands were calculated by the Lamarckian genetic algorithm (LGA). The docking results showed that the compounds SGQ4, DMUQ5, 6AUQ6, and PTQ8 had produced significant docking affinity for the protein tyrosine kinase with the binding energy of -7.46, -7.31, -6.85, and -6.74 kcal/mol, respectively, compared to the standard inhibitor Erlotinib (binding energy: -3.84 kcal/mol). Furthermore, molecular dynamics simulations (MDS) were performed using Gromacs to investigate the stability of a ligand-protein complex. The combined analysis of root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of 1M17 protein with docked ligands reveals that 1M17 protein has more stability when it interacts reacts with the inhibitor. Molecular descriptive properties and toxicity profile predicted by software. All the designed molecules passed Lipinski's rule of five successfully and they were found to be safe.
Keywords: Anilino quinazoline tyrosine kinase; Erlotinib; molecular docking; molecular dynamics simulation.