Download - Functions of Aquaporins in mammals
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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