title: Computational electrophysiology: the molecular dynamics of ion channel permeation and selectivity in atomistic detail.
abstract: Presently, most simulations of ion channel function rely upon nonatomistic Brownian dynamics calculations, indirect interpretation of energy maps, or application of external electric fields. We present a computational method to directly simulate ion flux through membrane channels based on biologically realistic electrochemical gradients. In close analogy to single-channel electrophysiology, physiologically and experimentally relevant timescales are achieved. We apply our method to the bacterial channel PorB from pathogenic Neisseria meningitidis, which, during Neisserial infection, inserts into the mitochondrial membrane of target cells and elicits apoptosis by dissipating the membrane potential. We show that our method accurately predicts ion conductance and selectivity and elucidates ion conduction mechanisms in great detail. Handles for overcoming channel-related antibiotic resistance are identified.
authors.affiliation: Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kutzner
authors.forename: Helmut
authors.initials: H
authors.lastname: Grubmüller
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zachariae
mesh_terms: D004352:Drug Resistance, Microbial / Q000235:genetics; D004553:Electric Conductivity; D055724:Electrophysiological Phenomena; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D007477:Ions; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation / Q000235:genetics; D009345:Neisseria meningitidis / Q000378:metabolism*; D010539:Permeability; D018272:Porins / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D007477:Ions; D008051:Lipid Bilayers; D018272:Porins; C057699:porin protein, Neisseria