Ion-dynamics in hepatitis C virus p7 helical transmembrane domains--a molecular dynamics simulation study

Area of Science:

• Biophysics
• Molecular Biology
• Virology

Background:

• Viral proteins self-assemble into homopolymers within infected cells.
• These protein structures can act as diffusion amplifiers for ions across cellular membranes.

Purpose of the Study:

• To investigate the dynamics of sodium, potassium, chloride, and calcium ions near the hepatitis C virus (HCV) protein p7 channel.
• To understand the role of histidine-17 in ion permeation through the p7 channel.

Main Methods:

• Constructing the HCV p7 protein bundle using docking and molecular dynamics (MD) simulations.
• Simulating 1M ion solutions for 200 nanoseconds to record ion dynamics.
• Analyzing the influence of histidine-17 protonation state on ion interactions.

Main Results:

• The histidine-17 residue was observed pointing into the p7 channel's lumen.
• Chloride ions entered the pore when histidine-17 was protonated; calcium ions entered when unprotonated.
• Applied voltage induced significant chloride ion currents, exhibiting rectification.

Conclusions:

• HCV p7 protein forms functional ion channels selective for specific ions based on residue protonation.
• The channel exhibits voltage-dependent properties and ion current rectification.
• Understanding p7 channel dynamics is crucial for viral function and potential therapeutic targets.