Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein.
Comput Biol Chem
; 64: 56-63, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27258799
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
Bibliotecas de Moléculas Pequenas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article