QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors

Title:QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors

Volume: 10 Issue: 1

Author(s): Hamdy I.A. Mostafa, Nihal. S. El-bialy, Ahmed A. Ezat, Noha. A. Saleh and Medhat A. Ibrahim

Affiliation:

Keywords: Docking, HCV, macrocyclic, NS3 protease, PM3, QSAR.

Abstract: Based on the N-terminal hexapeptide product of hydrolysis (EDVVCC) at HCV NS5A/5B junction, three modified groups of compounds are built. The first group contains linear peptides while the second and third groups contain P1-P3 and P2-P4 macrocyclic structures, respectively. Quantitative Structure Activity Relationship (QSAR) characterization and docking simulations are performed in order to investigate the potential of these compounds as HCV NS3/4A protease inhibitors. Based on the QSAR properties, the three most stable compounds due to their lowest total energy are P1-P3 and P2-P4 macrocycles of azahexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azahexapeptide sequence (DDIVP norvaline). They also have high surface area, solvent accessible surface area, volume, molar refractivity and polarizabilty. They have moderately low dipole moment and good log P values, as well. The docking scores of the best two P2-P4 macrocycles are just acceptable. The two compounds 5A/5B hexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azapentapeptide sequence (DIVP vinyl amino cyclopropane) yielded the best docking scores.

Cite this article as:

Mostafa I.A. Hamdy, El-bialy S. Nihal., Ezat A. Ahmed, Saleh A. Noha. and Ibrahim A. Medhat, QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors, Current Computer-Aided Drug Design 2014; 10 (1) . https://dx.doi.org/10.2174/15734099113096660048