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

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

Journal Name: Current Computer-Aided Drug Design

Volume 10 , Issue 1 , 2014

Become EABM
Become Reviewer


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.

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

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2014
Page: [28 - 40]
Pages: 13
DOI: 10.2174/15734099113096660048
Price: $65

Article Metrics

PDF: 29