TY - JOUR
T1 - Ion-dynamics in hepatitis C virus p7 helical transmembrane domains - A molecular dynamics simulation study
AU - Wang, Yi Ting
AU - Schilling, Roman
AU - Fink, Rainer H.A.
AU - Fischer, Wolfgang B.
N1 - Funding Information:
W.B.F. thanks the National Science Council ( NSC-98-2112-M-010-002-MY3 ), Taiwan, for financial support. R.F. thanks the German Excellence Initiative II — Global Networks for financial support. R.S. thanks the Heidelberg Medical School and the Baden-Württemberg Stiftung for a Ph.D. scholarship. We thank H.-J. Hsu, M.-H. Lin, M.M. Kalita and R.D. Mahato (Taipei, TW) for helpful discussions.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Computational modeling
KW - Conductance
KW - Ion channels
KW - Membrane protein
KW - Protein structure
UR - http://www.scopus.com/inward/record.url?scp=84903414882&partnerID=8YFLogxK
U2 - 10.1016/j.bpc.2014.06.001
DO - 10.1016/j.bpc.2014.06.001
M3 - Article
C2 - 24997299
AN - SCOPUS:84903414882
SN - 0301-4622
VL - 192
SP - 33
EP - 40
JO - Biophysical Chemistry
JF - Biophysical Chemistry
ER -
