title: Ion-dynamics in hepatitis C virus p7 helical transmembrane domains--a molecular dynamics simulation study.
abstract: 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 Ca(2+) 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 1M 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.
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, 112, Taiwan; Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Medical Biophysics Group, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Schilling
authors.affiliation: Medical Biophysics Group, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Rainer H A
authors.initials: RH
authors.lastname: Fink
authors.affiliation: Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, 112, Taiwan; Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, 112, Taiwan. Electronic address: wfischer@ym.edu.tw.
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Fischer
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D012984:Software; D014764:Viral Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D007477:Ions; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins
keywords: Computational modeling; Conductance; Ion channels; Membrane protein; Protein structure