title: Current state of theoretical and experimental studies of the voltage-dependent anion channel (VDAC).
abstract: Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane provides a controlled pathway for respiratory metabolites in and out of the mitochondria. In spite of the wealth of experimental data from structural, biochemical, and biophysical investigations, the exact mechanisms governing selective ion and metabolite transport, especially the role of titratable charged residues and interactions with soluble cytosolic proteins, remain hotly debated in the field. The computational advances hold a promise to provide a much sought-after solution to many of the scientific disputes around solute and ion transport through VDAC and hence, across the mitochondrial outer membrane. In this review, we examine how Molecular Dynamics, Free Energy, and Brownian Dynamics simulations of the large β-barrel channel, VDAC, advanced our understanding. We will provide a short overview of non-conventional techniques and also discuss examples of how the modeling excursions into VDAC biophysics prospectively aid experimental efforts. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: Department of Biological Sciences and Centre for Molecular Simulation, University of Calgary, 2500 University Drive N.W., Calgary, Alberta T2N1N4, Canada. Electronic address: snoskov@ucalgary.ca.
authors.forename: Sergei Yu
authors.initials: SY
authors.lastname: Noskov
authors.affiliation: Section on Molecular Transport, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rostovtt@mail.nih.gov.
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Rostovtseva
authors.affiliation: Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Chamberlin
authors.affiliation: Section on Molecular Transport, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Department of Medical Epigenetics, Institute of Medical Sciences and Genomic Medicine, EuroEspes Sta. Marta de Babío S/N, 15165 Bergondo, A Coruña, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Teijido
authors.affiliation: Leadership Computing Facility, Argonne National Laboratory, 9700S Cass Avenue, Lemont, IL 60439, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Section on Molecular Transport, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: bezrukos@mail.nih.gov.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Bezrukov
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D015640:Ion Channel Gating; D008928:Mitochondria / Q000737:chemistry* / Q000648:ultrastructure; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D050994:Voltage-Dependent Anion Channels
keywords: Beta-barrel channel reconstitution; Brownian Dynamics simulations; Mitochondrial transport; Molecular Dynamics simulations; VDAC; pH regulation