Hydrogen Bond Stability of Quinazoline Derivatives Compounds in Complex against EGFR using Molecular Dynamics Simulation

Abstract

Lung cancer was a second common cancer case due to the high cigarette smoking activity both in men and women. One of protein receptor which plays an important role in the growth of the tumor is Epidermal Growth Factor Receptor (EGFR). EGFR protein is the most frequent protein mutation in cancer and promising target to inhibit the cancer growth. In this work, the stability of the hydrogen bond as the main interaction in the inhibition mechanism of cancer will be evaluated using molecular dynamics simulation. There were two compounds (A1 and A2) as new potential inhibitors that were complexed against the EGFR protein. The dynamic properties of each complexed were compared with respect to erlotinib against EGFR. The result revealed that both compounds had an interaction in the main catalytic area of protein receptor which is at methionine residue. Inhibitor A1 showed additional interactions during simulation time but the interactions tend to be weak. Inhibitor A2 displayed a more stable interaction. Following dynamics simulation, binding free energy calculation was performed by two scoring techniques MM/GB(PB)SA method and gave a good correlation with the stability of the complex. Furthermore, potential inhibitor A2 had a lower binding free energy as a direct consequence of the stability of hydrogen bond interaction.

Design of New Quinazoline Derivative as EGFR (Epidermal Growth Factor Receptor) Inhibitor through Molecular Docking and Dynamics Simulation

“…The advantage of molecular docking in designing a new inhibitor does not require a large amount of data or only employ some molecules as the lead compounds. Previous research had designed quinazoline derivative compounds by using quantitative structureactivity relationship (QSAR) analysis in large data compounds [16][17][18] and studied the stability of hydrogen bond formed through compound and protein [19][20][21][22]. However, designing a new EGFR inhibitor using a molecular docking approach of the lead compounds such as erlotinib, afatinib, and WZ4002 has never been done.…”

Molecular Docking and Molecular Dynamic Investigations of Xanthone-Chalcone Derivatives against Epidermal Growth Factor Receptor for Preliminary Discovery of Novel Anticancer Agent

“…Computer-aided drug design offers a powerful tool to design and screen new chemotherapy agents [6][7]. In this in silico assay, the crystalline structure of protein receptors inside the cancer cells is modeled and simulated in the presence of a new chemotherapy agent [8].…”