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

•Generation of hexameric assemblies of ion channel forming p7 of HCV•Protonation of His-17 allows Cl-ions to enter the pore.•In unprotonated bundle also Ca-ions are found within the pore.•Applied voltage identifies large Cl-ion currents from the site of the loop.•Slight rectification of the current is observed.

Viral proteins assemble into homopolymers in the infected cells and have a role as diffusion-amplifier for ions across subcellular membranes. The homopolymer of hepatitis C virus, protein p7 of strain 1a, which is known to form channels, is used to investigate the dynamics of physiological relevant ions, Na+, K+, Cl− and Ca2+ in the vicinity of the protein bundle. The protein bundle is generated by a combination of docking approach and molecular dynamics (MD) simulations. Ion dynamics are recorded during multiple 200 ns MD simulations of 1 M solutions. His-17 is found to point into the lumen of the pore. Protonation of this residue allows Cl-ions to enter the pore while in its unprotonated state Ca-ions are found within the pore as well. Applied voltage identifies large Cl-ion currents from the site of the loop passing through the pore. Rectification of the current of the Cl-ions is observed.

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