functions of aquaporins in mammals
DESCRIPTION
Functions of Aquaporins in mammals. Nephron. The role of Aquaporins in the kidney. Kidney. Cortex. proximal tubules. collecting duct. Aqp0. urine concentration reabsorption of water into blood. Aqp0. The role of Aquaporins in the kidney. monomers. tetramers. - PowerPoint PPT PresentationTRANSCRIPT
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Functions of Aquaporinsin mammals
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Kidney Cortex
Nephron
proximal tubules collecting duct
Aqp0Aqp0 urine concentration
reabsorption of water into blood
The role of Aquaporins in the kidney
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The role of Aquaporins in the kidney
tetramers
monomers
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Glycerol Channel and the Aquaporin Family
water transport in cells: aquaporins
water+glycerol transport:aquaglycoporins
ions and charged solutes excludedfrom transport
tetrameric architecture
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GlpF Simulation: Advanced and large scale
full electrostatics (PME),periodic boundary conditionsNpT ensemble at 310 K1 ns equilibration
protein ~ 15,000 atomslipids ~ 40,000 atomswater ~ 51,000 atomsall ~ 106,000 atoms
2002: 12 days/ns – 64 T3E CPU
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Note the curved adjustment between lipids and protein
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Competition of water and glycerol for H-bonds
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Simulated System 2:
GlpF with one glycerolper channel: initial state
GlpF with one glycerolper channel: after 1ns
entire conduction event needs to be enforced
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Steered MD simulation of glycerol passage through GlpF
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Challenge: Quantitative analysis of SMD
potential of mean force (PMF) isreconstructed from time series ofapplied force and displacement
non-equilibrium analysis based on Langevin equation:
multiple trajectories can becombined to yield statisticallysignificant results
But: one needs to discount irreversible work!
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Constructing the potential of mean force
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Potential of mean force along channel axis
attractive extra-cellular vestibule
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Simulated system 3: GlpF with only water
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GlpF crystallography without glycerol
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Water arrangement in GlpF
fromx-raydiffract.
at 100K
from MD
at 300K
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orientation
diffusion
Bipolar orientation and diffusion of water through GlpF
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Filtering mechanism in GlpF
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Correlatedwater dynamicsin the channel
correlated displacementof waters in channel
water pair correlation
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Aquaporin: seeing waters in motion
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p=0 p>0 p<0
Pressure-induced water conduction in GlpF
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Pressure-induced water conduction in GlpF