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.
Original language | English |
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Article number | 324 |
Pages (from-to) | 1-14 |
Number of pages | 14 |
Journal | SpringerPlus |
Volume | 2 |
Issue number | 1 |
DOIs | |
State | Published - 2013 |
Keywords
- Docking approach
- HCV
- Ion channels
- Membrane protein
- Molecular dynamics simulations
- p7 protein