title: Molecular dynamics studies of ion permeation in VDAC.
abstract: The voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria serves an essential role in the transport of metabolites and electrolytes between the cell matrix and mitochondria. To examine its structure, dynamics, and the mechanisms underlying its electrophysiological properties, we performed a total of 1.77 μs molecular dynamics simulations of human VDAC isoform 1 in DOPE/DOPC mixed bilayers in 1 M KCl solution with transmembrane potentials of 0, ±25, ±50, ±75, and ±100 mV. The calculated conductance and ion selectivity are in good agreement with the experimental measurements. In addition, ion density distributions inside the channel reveal possible pathways for different ion species. Based on these observations, a mechanism underlying the anion selectivity is proposed; both ion species are transported across the channel, but the rate for K(+) is smaller than that for Cl(-) because of the attractive interactions between K(+) and residues on the channel wall. This difference leads to the anion selectivity of VDAC.
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas.
authors.forename: Huan
authors.initials: H
authors.lastname: Rui
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas.
authors.forename: Kyu Il
authors.initials: KI
authors.lastname: Lee
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Pastor
authors.affiliation: Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas. Electronic address: wonpil@ku.edu.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
mesh_terms: D004058:Diffusion; D055724:Electrophysiological Phenomena; D006801:Humans; D007477:Ions / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010539:Permeability; D016062:Porosity; D055672:Static Electricity; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007477:Ions; D008051:Lipid Bilayers; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1