Laasch, N, Kalita, MM, Griffin, S orcid.org/0000-0002-7233-5243 et al. (1 more author) (2016) Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein. Computational Biology and Chemistry, 64. pp. 56-63. ISSN 1476-9271
Abstract
The genome of hepatitis C virus encodes for an essential 63 amino acid polytopic protein p7 of most likely two transmembrane domains (TMDs). The protein is identified to self-assemble thereby rendering lipid membranes permeable to ions. A series of small molecules such as adamantanes, imino sugars and guanidinium compounds are known to interact with p7. A set of 9 of these small molecules is docked against hexameric bundles of genotypes 5a (bundle-5a) and 1b (bundle-1b) using LeadIT. Putative sites for bundle-5a are identified within the pore and at pockets on the outside of the bundle. For bundle-1b preferred sites are found at the site of the loops. Binding energies are in favour of the guanidinium compounds. Rescoring of the identified poses with HYDE reveals a dehydration penalty for the guanidinium compounds, leaving the adamantanes and imino sugar in a better position. Binding energies calculated by HYDE and those by LeadIT indicate that all compounds are moderate binders.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | p7 of HCV; Antivirals; Guanidinium compounds; Adamantanes; Imino sugars; Docking approach; MD simulations |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Jul 2016 15:49 |
Last Modified: | 03 Nov 2016 05:58 |
Published Version: | http://dx.doi.org/10.1016/j.compbiolchem.2016.04.0... |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.compbiolchem.2016.04.010 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101728 |