Searching for anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors through a combination of molecular docking, 3D-QSAR and virtual screening. (2nd January 2016)

• Record Type: Journal Article
• Authors: Vrontaki, Eleni; Melagraki, Georgia; Mavromoustakos, Thomas; Afantitis, Antreas
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 1(2016:Feb.)
• Page Start: 38
• Page End: 52
• Publication Date: 2016-01-02
• Subjects: 3D-QSAR CoMFA -- HCV replication inhibitors -- molecular docking -- PubChem database -- virtual screening; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2014.1003925
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A combination of the following computational methods: (i) molecular docking, (ii) 3-D Quantitative Structure Activity Relationship Comparative Molecular Field Analysis (3D-QSAR CoMFA), (iii) similarity search and (iv) virtual screening using PubChem database was applied to identify new anthranilic acid-based inhibitors of hepatitis C virus (HCV) replication. A number of known inhibitors were initially docked into the "Thumb Pocket 2" allosteric site of the crystal structure of the enzyme HCV RNA-dependent RNA polymerase (NS5B GT1b). Then, the CoMFA fields were generated through a receptor-based alignment of docking poses to build a validated and stable 3D-QSAR CoMFA model. The proposed model can be first utilized to get insight into the molecular features that promote bioactivity, and then within a virtual screening procedure, it can be used to estimate the activity of novel potential bioactive compounds prior to their synthesis and biological tests.