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.
Keywords: Docking, HCV, macrocyclic, NS3 protease, PM3, QSAR.
Current Computer-Aided Drug Design
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/15734099113096660048 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Combined Cancer Therapy: Strategies to Overcome Acquired Aromatase Inhibitor Resistance
Current Pharmaceutical Design The Effects of Fusion Structure on the Expression and Bioactivity of Human Brain Natriuretic Peptide (BNP) Albumin Fusion Proteins
Current Pharmaceutical Biotechnology Genetic Polymorphisms of Drug Metabolising Enzymes and Drug Transporters in Relation to Cancer Risk
Current Cancer Therapy Reviews Role of COL4A1 in Basement-Membrane Integrity and Cerebral Small-Vessel Disease. The COL4A1 Stroke Syndrome
Current Medicinal Chemistry Hyperferritinaemia: An Iron Sword of Autoimmunity
Current Pharmaceutical Design The Escalating Challenge of Vancomycin Resistance in Staphylococcus aureus
Current Drug Targets - Infectious Disorders Estrogens as Potential Therapeutic Agents in Multiple Sclerosis
Central Nervous System Agents in Medicinal Chemistry Anti-Platelet Treatment of Middle-Sized Abdominal Aortic Aneurysms
Current Vascular Pharmacology Hepatic Encephalopathy: Cause and Possible Management with Botanicals
Recent Patents on Inflammation & Allergy Drug Discovery The Role of Signaling Pathway in the Biological Cause of Rheumatoid Arthritis
Current Drug Research Reviews Targets of Antidementive Therapy: Drugs with a Specific Pharmacological Mechanism of Action
Current Pharmaceutical Design Overlapping Molecular Signatures in Parkinson's Patient Leukocytes Before and After Treatment and in Mouse Model Brain Regions
CNS & Neurological Disorders - Drug Targets Dietary Small Molecules and Large-Scale Gene Expression Studies: An Experimental Approach for Understanding their Beneficial Effects on the Development of Malignant and Non-Malignant Proliferative Diseases
Current Medicinal Chemistry Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases
CNS & Neurological Disorders - Drug Targets Review of Chemoradiotherapy for High-Risk Prostate Cancer
Reviews on Recent Clinical Trials High Mobility Group Box 1 Protein as a Potential Drug Target for Infection- and Injury-Elicited Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Antibody-Based Therapies in Systemic Lupus Erythematosus
Mini-Reviews in Medicinal Chemistry Alzheimer's Disease: Emerging Trends in Small Molecule Therapies
Current Medicinal Chemistry Water-soluble Complex of Curcumin with Cyclodextrins: Enhanced Physical Properties For Ocular Drug Delivery
Current Drug Delivery Current Strategies of Tissue Engineering in Talus Chondral Defects
Current Stem Cell Research & Therapy