Protein-protein interactions: modeling the hepatitis C virus ion channel p7

J Med Chem. 2006 Jan 26;49(2):648-55. doi: 10.1021/jm050721e.


The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure prediction algorithms and is proposed to span from Ala-10 to Leu-32 for TM1 and from Trp-36 to Pro-58 for TM2. A configurational search protocol based on simulated annealing combined with short restrained molecular dynamics simulations is used in addition to protein-protein docking to investigate the packing of TM1/TM2. Full p7 oligomeric bundles were generated, and in the most plausible models serines and threonines are facing the hydrophilic pore. In these models, His-17 would be a pore-facing residue, suggesting that p7 may be sensitive to pH in respect to its function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / chemistry
  • Amino Acid Sequence
  • Antiviral Agents / chemistry
  • Hepacivirus*
  • Ion Channels / chemistry*
  • Membrane Proteins / chemistry*
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptides / chemistry
  • Protein Binding
  • Protein Structure, Secondary
  • Sequence Alignment
  • Thermodynamics
  • Viral Proteins / chemistry*


  • Antiviral Agents
  • Ion Channels
  • Membrane Proteins
  • Peptides
  • Viral Proteins
  • p7 protein, Hepatitis C virus
  • Amantadine