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.
Original language | English |
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Pages (from-to) | 56-63 |
Number of pages | 8 |
Journal | Computational Biology and Chemistry |
Volume | 64 |
DOIs | |
State | Published - 1 Oct 2016 |
Keywords
- Adamantanes
- Antivirals
- Docking approach
- Guanidinium compounds
- Imino sugars
- MD simulations
- p7 of HCV