Current Computer Aided-Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


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 and Medhat A. Ibrahim

Affiliation: Biophysics Department, Faculty of Science, University of Cairo, Giza, Egypt.

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


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.

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Article Details

Page: [28 - 40]
Pages: 13
DOI: 10.2174/15734099113096660048