title: Simulations of outer membrane channels and their permeability.
abstract: Channels in the outer membrane of Gram-negative bacteria provide essential pathways for the controlled and unidirectional transport of ions, nutrients and metabolites into the cell. At the same time the outer membrane serves as a physical barrier for the penetration of noxious substances such as antibiotics into the bacteria. Most antibiotics have to pass through these membrane channels to either reach cytoplasmic bound targets or to further cross the hydrophobic inner membrane. Considering the pharmaceutical significance of antibiotics, understanding the functional role and mechanism of these channels is of fundamental importance in developing strategies to design new drugs with enhanced permeation abilities. Due to the biological complexity of membrane channels and experimental limitations, computer simulations have proven to be a powerful tool to investigate the structure, dynamics and interactions of membrane channels. Considerable progress has been made in computer simulations of membrane channels during the last decade. The goal of this review is to provide an overview of the computational techniques and their roles in modeling the transport across outer membrane channels. A special emphasis is put on all-atom molecular dynamics simulations employed to better understand the transport of molecules. Moreover, recent molecular simulations of ion, substrate and antibiotics translocation through membrane pores are briefly summarized. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Karunakar R
authors.initials: KR
authors.lastname: Pothula
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Carlos J F
authors.initials: CJ
authors.lastname: Solano
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kleinekathöfer
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D004058:Diffusion; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000648:ultrastructure; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000648:ultrastructure*; D008051:Lipid Bilayers / Q000737:chemistry; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D007473:Ion Channels; D008051:Lipid Bilayers
keywords: Antibiotics; Free-energy calculations; Molecular dynamics simulations; Outer membrane channels; Translocation