title: The mechanism of proton exclusion in aquaporin channels.
abstract: The mechanism of proton exclusion in aquaporin channels is elucidated through free energy calculations of the pathway of proton transport. The second generation multistate empirical valence bond (MS-EVB2) model was applied to simulate the interaction of an excess proton with the channel environment. Jarzynski's equality was employed for rapid convergence of the free energy profile. A barrier sufficiently high to block proton transport is located near the channel center at the NPA motif-a site involved in bi-orientational ordering of the embedded water-wire in absence of the excess proton. A second and lower barrier is observed at the selectivity filter near the periplasmic outlet where the channel is narrowest. This secondary barrier may be essential in filtering other large solutes and cations.
authors.affiliation: Department of Chemistry and Henry Eyring Center for Theoretical Chemistry, University of Utah, Salt Lake City, Utah 84112-0850, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: Ilan
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism*; D001692:Biological Transport; D002412:Cations / Q000378:metabolism; D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D011522:Protons; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D002412:Cations; D029968:Escherichia coli Proteins; D011522:Protons; D014867:Water; C078043:GlpF protein, E coli