Computational modeling of the p7 monomer from HCV and its interaction with small molecule drugs

Wang, Yi-Ting; Hsu, Hao-Jen; Fischer, Wolfgang B

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 TMD1(1-32) and a region around Gly-46 to Trp-48 for TMD2(36-58). Mutations of the tyrosine residues in TMD2(36-58) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-324) contains supplementary material, which is available to authorized users.