title: Computational modeling of the p7 monomer from HCV and its interaction with small molecule drugs.
abstract: Hepatitis C virus p7 protein is a 63 amino acid polytopic protein with two transmembrane domains (TMDs) and one of the prime targets for anti HCV drug development. A bio-inspired modeling pathway is used to generate plausible computational models of the two TMDs forming the monomeric protein model. A flexible region between Leu-13 and Gly-15 is identified for TMD11-32 and a region around Gly-46 to Trp-48 for TMD236-58. Mutations of the tyrosine residues in TMD236-58 into phenylalanine and serine are simulated to identify their role in shaping TMD2. Lowest energy structures of the two TMDs connected with the loop residues are used for a posing study in which small molecule drugs BIT225, amantadine, rimantadine and NN-DNJ, are identified to bind to the loop region. BIT225 is identified to interact with the backbone of the functionally important residues Arg-35 and Trp-36.
authors: Department of Life Science, Tzu Chi University, Hualien, 970 Taiwan.
authors: Yi-Ting
authors: YT
authors: Wang
authors: Hao-Jen
authors: HJ
authors: Hsu
authors: Wolfgang B
authors: WB
authors: Fischer
keywords: Docking approach; HCV; Ion channels; Membrane protein; Molecular dynamics simulations; p7 protein
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