کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
15093 | 1374 | 2014 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Docking assay of small molecule antivirals to p7 of HCV Docking assay of small molecule antivirals to p7 of HCV](/preview/png/15093.png)
• Binding poses of antivirals to monomers and hexameric bundles of p7 of HCV.
• Guanidine based ligands bind better than derivatives of adamantanes and iminosugars.
• Binding of the best candidates is at the site of the loop.
• Hydrogen bonding and hydrophobic interactions are important.
Protein p7 of HCV is a 63 amino acid channel forming membrane protein essential for the progression of viral infection. With this momentousness, p7 emerges as an important target for antiviral therapy. A series of small molecule drugs, such as amantadine, rimantadine, amiloride, hexamethylene amiloride, NN-DNJ and BIT225 have been found to affect the channel activity. These compounds are docked against monomeric and hexameric structures of p7 taken at various time steps from a molecular dynamics simulation of the protein embedded in a hydrated lipid bilayer. The energetics of binding identifies the guanidine based ligands as the most potent ligands. The adamantanes and NN-DNJ show weaker binding energies. The lowest energy poses are those at the site of the loop region for the monomer and hexamer. For the latter, the poses show a tendency of the ligand to face the lumen of the pore. The mode of binding is that of a balance between hydrophobic interactions and hydrogen bond formation with backbone atoms of the protein.
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Journal: Computational Biology and Chemistry - Volume 53, Part B, December 2014, Pages 308–317