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