title: Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF.
abstract: "Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.
authors.affiliation: Theoretical Molecular Biophysics Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: B L
authors.initials: BL
authors.lastname: de Groot
authors.forename: H
authors.initials: H
authors.lastname: Grubmüller
mesh_terms: D020816:Amino Acid Motifs; D051398:Aquaporin 1; D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins; D005990:Glycerol / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers; D008564:Membrane Potentials; D008954:Models, Biological; D008958:Models, Molecular; D010539:Permeability; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011522:Protons; D055672:Static Electricity; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; D011522:Protons; D014867:Water; C078043:GlpF protein, E coli; D051398:Aquaporin 1; D005990:Glycerol