title: Docking assay of small molecule antivirals to p7 of HCV.
abstract: 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.
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei 112, Taiwan, ROC.
authors.forename: Leon
authors.initials: L
authors.lastname: Bichmann
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei 112, Taiwan, ROC.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei 112, Taiwan, ROC. Electronic address: wfischer@ym.edu.tw.
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
keywords: Antivirals; Docking; MD simulations; p7 of HCV