Aquaporins (AQPs) are a family of integral membrane proteins, which facilitate the rapid and yet highly selective flux of water and other small solutes across biological membranes. Molecular dynamics (MD) simulations contributed substantially to the understanding of the molecular mechanisms that underlie this remarkable efficiency and selectivity of aquaporin channels. This chapter reviews the current state of MD simulations of aquaporins and related aquaglyceroporins as well as the insights these simulations have provided. The mechanism of water permeation through AQPs and methods to determine channel permeabilities from simulations are described. Protons are strictly excluded from AQPs by a large electrostatic barrier and not by an interruption of the Grotthuss mechanism inside the pore. Both the protein's electric field and desolvation effects contribute to this barrier. Permeation of apolar gas molecules such as CO2 through AQPs is accompanied by a large energetic barrier and thus can only be expected in membranes with a low intrinsic gas permeability. Additionally, the insights from simulations into the mechanism of glycerol permeation through the glycerol facilitator GlpF from E. coli are summarized. Finally, MD simulations are discussed that revealed that the aro-matic/arginine constriction region is generally the filter for uncharged solutes, and that AQP selectivity is controlled by a hydrophobic effect and steric restraints.
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References
Beitz E, Wu B, Holm LM, Schultz JE, Zeuthen T (2006) Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons. Proc Natl Acad Sci USA 103:269–274
Blank ME, Ehmke H (2003) Aquaporin-1 and HCO3(−)−Cl(−) transporter-mediated transport of CO2 across the human erythrocyte membrane. J Physiol 550:2:419–429
Borgnia MJ, Agre P (2001) Recontitution and functional comparison of purified GlpF and AqpZ, the glycerol and water channels from Eschericia coli. Proc Natl Acad Sci USA 98:2888–2893
Burykin A, Warshel A (2003) What really prevents proton transport through aquaporin? Charge self-energy versus proton wire proposals. Biophys1 J 85:3696–3706
Burykin A, Warshel A (2004) On the origin of the electrostatic barrier for proton transport in aquaporin. FEBS Lett 570:41–46
Chakrabarti N, Roux B, Pomes R (2004a) Structural determinants of proton blockage in aquapor-ins. J Mol Biol 343:493–510
Chakrabarti N, Tajkhorshid E, Roux B, Pomes R (2004b) Molecular basis of proton blockage in aquaporins. Structure 12:65–74
Chen H, Wu Y, Voth GA (2006) Origins of proton transport behavior from selectivity domain mutations of the aquaporin-1 channel. Biophys J 90:L73–L75
Cooper GJ, Boron WF (1998) Effect of PCMBS on CO2 permeability of Xenopus oocytes expressing aquaporin 1 or its C189S mutant. Am J Physiol 275:C1481–C1486
de Groot BL, Grubmüller H (2001) Water permeation across biological membranes:mechanism and dynamics of aquaporin-1 and GlpF. Science 294:2353–2357
de Groot BL, Grubmüller H (2005) The dynamics and energetics of water permeation and proton exclusion in aquaporins. Curr Opin Struct Biol 15:176–183
de Groot BL, Engel A, Grubmüller H (2001) A refined structure of human Aquaporin-1. FEBS Lett 504:206–211
de Groot BL, Tieleman DP, Pohl P, Grubmüller H (2002) Water permeation through gramicidin A:desformylation and the double helix; a molecular dynamics study. Biophys J. 82:2934–2942
de Groot BL, Frigato T, Helms V, Grubmüller H (2003) The mechanism of proton exclusion in the aquaporin-1 water channel. J Mol Biol 333:279–293
de Grotthuss CJT (1806) Sur la décomposition de l'eau et des corps qu'elle tient en dissolution à l'aide de l'électricité galvanique. Ann Chim LVIII:54–74
Endeward V, Musa-Aziz R, Cooper GJ, Chen L-M, Pelletier MF, Virkki LV, Supuran CT, King LS, Boron WF, Gros G (2006) Evidence that aquaporin 1 is a major pathway for CO2 transport across the human erythrocyte membrane. FASEB J 20:1974–1981
Engel A, Stahlberg H (2002) Aquaglyceroporins: channel proteins with a conserved core, multiple functions and variable surfaces. Int. Rev. Cytol.215:75–104
Fang X, Yang B, Matthay MA, Verkman AS (2002) Evidence against aquaporin-1-dependent CO2 permeability in lung and kidney. J Physiol 542:63–69
Finkelstein A (1987) Water movement through lipid bilayers, pores, and plasma membranes. Wiley, New York
Fu D, Libson A, Miercke LJ, Weitzman C, Nollert P, Krucinski J, Stroud RM (2000) Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290:481–486
Gonen T, Sliz P, Kistler J, Cheng Y, Walz T (2004) Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature 429:193–197
Hashido M, Ikeguchi M, Kidera A (2005) Comparative simulations of aquaporin family: AQP1, AQPZ, AQP0 and GlpF. FEBS Lett 579:5549–5552
Hashido M, Kidera A, Ikeguchi M (2007) Water transport in aquaporins: osmotic permeability matrix analysis of molecular dynamics simulations. Biophys J 93:373–385
Heller KB, Lin EC, Wilson TH (1980) Substrate-specificity and transport-properties of the glycerol facilitator of Eschericia coli. J Bacteriol 144:274–278
Hénin J, Tajkhorshid E, Schulten K, Chipot C (2008) Diffusion of glycerol through Escherichia coli aquaglyceroporin GlpF. Biophys J 94:832–839
Heymann JB, Engel A (2000) Structural clues in the sequences of the aquaporins. J Mol Biol 295:1039–1053
Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, Walz T, Sasaki S, Mitsuoka K, Kimura K, Mizoguchi A, Fujiyoshi Y (2006) Implications of the aquaporin-4 structure on array formation and cell adhesion. J Mol Biol 355:625–639
Holm LM, Jahn TP, Møller ALB, Schjoerring JK, Ferri D, Klaerke DA, Zeuthen T (2005) NH3 and NH4 + permeability in aquaporin-expressing Xenopus oocytes. Pflugers Arch 450:415–428
Hub JS, de Groot BL (2006) Does CO2 permeate through Aquaporin-1? Biophys J 91:842–848
Hub JS, de Groot BL (2008) Mechanism of selectivity in aquaporins and aquaglyceroporins. Proc Natl Acad Sci USA 105:1198–1203
Ilan B, Tajkhorshid E, Schulten K, Voth GA (2004) The mechanism of proton exclusion in aqua-porin channels. Proteins 55:223–228
Jensen MØ, Mouritsen OG (2006) Single-channel water permeabilities of Escherichia coli aqua-porins AqpZ and GlpF. Biophys J 90:2270–2284
Jensen MØ, Tajkhorshid E, Schulten K (2001) The mechanism of glycerol conduction in aquaglyc-eroporins. Structure 9:1083–1093
Jensen MØ, Park S, Tajkhorshid E, Schulten K (2002) Energetics of glycerol conduction through aquaglyceroporin GlpF. Proc Natl Acad Sci USA 99:6731–6736
Jensen MØ, Tajkhorshid E, Schulten K (2003) Electrostatic tuning of permeation and selectivity in aquaporin water channels. Biophys J 85:2884–2899
Jung JS, Preston GM, Smith BL, Guggino WB, Agre P (1994) Molecular structure of the water channel through aquaporin CHIP — the hourglass model. J Biol Chem 269:14648–14654
Kato M, Pisliakov AV, Warshel A (2006) The barrier for proton transport in aquaporins as a challenge for electrostatic models: the role of protein relaxation in mutational calculations. Proteins 64:829–844
Lee JK, Kozono D, Remis J, Kitagawa Y, Agre P, Stroud RM (2005) Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A. Proc Natl Acad Sci USA 102:18932–18937
Maurel C, Reizer J, Schroeder JI, Chrispeels MJ, Saier MH (1994) Functional characterization of the Eschericia coli glycerol facilitator, GlpF, in Xenopus oocytes. J Biol Chem 269: 11869–11872
Murata K, Mitsuoka K, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature 407:599–605
Nakhoul NL, Davis BA, Romero MF, Boron WF (1998) Effect of expressing the water channel aquaporin-1 on the CO2 permeability of Xenopus oocytes. Am J Physiol Cell Physiol 274:C543–C548
Prasad GVR, Coury LA, Finn F, Zeidel ML (1998) Reconstituted aquaporin 1 water channels transport co2 across membranes. J Biol Chem 273:33123–33126
Preston GM, Carroll TP, Guggino WB, Agre P (1992) Appearance of water channels in Xenopus oocytes expressing red-cell CHIP28 protein. Science 256:385–387
Savage DF, Egea PF, Robles-Colmenares Y, O'Connell JDI, Stroud RM (2003) Architecture and selectivity in aquaporins:2.5Å X-ray structure of aquaporin Z. PLoS Biol. 1:e72
Sui H, Han B-G, Lee JK, Walian P, Jap BK (2001) Structural basis of water-specific transport through the AQP1 water channel. Nature 414:872–878
Tajkhorshid E, Nollert P, Jensen MØ, Miercke LJW, O'Connell J, Stroud RM, Schulten K (2002) Control of the selectivity of the aquaporin water channel family by global orientational tuning. Science 296:525–530
Törnroth-Horsefield S, Wang Y, Hedfalk K, Johanson U, Karlsson M, Tajkhorshid E, Neutze R, Kjellbom P (2006) Structural mechanism of plant aquaporin gating. Nature 439:688–694
Torrie GM, Valleau JP (1974) Monte Carlo free energy estimates using non-Boltzmann sampling: application to the sub-critical Lennard-Jones fluid. Chem Phys Lett 28:578–581
Uehlein N, Lovisolo C, Siefritz F, Kaldenhoff R (2003) The tobacco aquaporin NtAQP1 is a membrane CO2 pore with physiological functions. Nature 425:734–737
Wang Y, Schulten K, Tajkhorshid E (2005) What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF. Structure 13:1107–1118
Wang Y, Cohen J, Boron WF, Schulten K, Tajkhorshid E (2007) Exploring gas permeability of cellular membranes and membrane channels with molecular dynamics. J Struct Biol 157: 534–544
Yang B, Fukuda N, van Hoek A, Matthay MA, Ma T, Verkman AS (2000) Carbon dioxide permeability of aquaporin-1 measured in erythrocytes and lung of aquaporin-1 null mice and in reconstituted proteoliposomes. J Biol Chem 275:2686–2692
Zardoya R (2005) Phylogeny and evolution of the major intrinsic protein family. Biol Cell 97: 397–414
Zeidel ML, Ambudkar SV, Smith BL, Agre P (1992) Reconstitution of functional water channels in liposomes containing purified red-cell CHIP28 protein. Biochemistry 31:7436–7440
Zeidel ML, Nielsen S, Smith BL, Ambudkar SV, Maunsbach AB, Agre P (1994) Ultrastructure, pharmacological inhibition, and transport selectivity of aquaporin channel-forming integral protein in proteoliposomes. Biochemistry 33:1606–1615
Zhu F, Tajkhorshid E, Schulten K (2002) Pressure-induced water transport in membrane channels studied by molecular dynamics. Biophys J 83:154–160
Zhu F, Tajkhorshid E, Schulten K (2004a) Collective diffusion model for water permeation through microscopic channels. Phys Rev Lett 93:224501
Zhu F, Tajkhorshid E, Schulten K (2004b) Theory and simulation of water permeation in aquaporin-1. Biophys J 86:50–57
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Hub, J.S., Grubmüller, H., de Groot, B.L. (2009). Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?. In: Beitz, E. (eds) Aquaporins. Handbook of Experimental Pharmacology, vol 190. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79885-9_3
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