Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein.

Comput Biol Chem

Institute of Biophotonics, School of Biomedical Science and Engineering, and Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan. Electronic address:

Published: October 2016

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiolchem.2016.04.010DOI Listing

Publication Analysis

Top Keywords

guanidinium compounds
12
hepatitis virus
8
small molecules
8
adamantanes imino
8
binding energies
8
small molecule
4
molecule ligand
4
ligand docking
4
docking genotype
4
genotype specific
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!