title: Dynamics and energetics of water permeation through the aquaporin channel.
abstract: Structural properties of water inside bovine aquaporin-1 are investigated by molecular simulation. The calculations, which are based on the recently determined X-ray structure at 2.2 A resolution (Sui et al., Nature 2001;414:872-878), are carried out on one monomeric subunit immersed in a water-n-octane-water bilayer. Molecular dynamics (MD) simulations suggest that His182, a fully conserved residue in the channel pore, is protonated in the delta position. Furthermore, they reveal a highly ordered water structure in the channel, induced by the electrostatic properties of the protein. Multiple-steering MD simulations are used to calculate the free-energy of water diffusion. To the best of our knowledge, this represents the first free-energy calculation based on the new, high-resolution structure of the pore. The calculated barrier is 2.5 kcal/mol, and it is associated to water permeation through the Asn-Pro-Ala (NPA) region of the pore, where water molecules are only hydrogen-bonded with themselves. These findings are fully consistent with those based on the previous MD studies on the human protein (de Groot and Grubmüller, Science 2001;294:2353-2357).
authors.affiliation: International School for Advanced Studies, S.I.S.S.A. and INFM-Democritos Modeling Center for Research In Atomistic Simulation, Trieste, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Vidossich
authors.forename: Michele
authors.initials: M
authors.lastname: Cascella
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D003198:Computer Simulation; D004058:Diffusion; D006639:Histidine / Q000737:chemistry; D008958:Models, Molecular; D010539:Permeability; D011522:Protons; D055672:Static Electricity; D014867:Water / Q000737:chemistry*
chemical_list: D020346:Aquaporins; D011522:Protons; D014867:Water; D051398:Aquaporin 1; D006639:Histidine