title: QSAR analysis and molecular docking simulation of suggested peptidomimetic NS3 protease inhibitors.
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.
authors.forename: Hamdy I A
authors.initials: HI
authors.lastname: Mostafa
authors.forename: Nihal S
authors.initials: NS
authors.lastname: El-bialy
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Ezat
authors.forename: Noha A
authors.initials: NA
authors.lastname: Saleh
authors.affiliation: Biophysics Department, Faculty of Science, University of Cairo, Giza, Egypt. noha_saleh_kh@yahoo.com.
authors.forename: Medhat A
authors.initials: MA
authors.lastname: Ibrahim
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D004735:Energy Transfer; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D008958:Models, Molecular; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases