Functions of Aquaporins

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Functions of Aquaporins in mammals
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Nephron
The role of Aquaporins in the kidney
Kidney
Cortex
proximal tubules
collecting duct
Aqp0
urine concentration reabsorption of water into
blood
Aqp0
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The role of Aquaporins in the kidney
monomers
tetramers
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Glycerol Channel and the Aquaporin Family
water transport in cells aquaporins waterglycer
ol transport aquaglycoporins ions and charged
solutes excluded from transport tetrameric
architecture
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GlpF Simulation Advanced and large scale
full electrostatics (PME), periodic boundary
conditions NpT ensemble at 310 K 1 ns
equilibration protein 15,000 atoms lipids
40,000 atoms water 51,000 atoms all 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 glycerol per channel initial state
GlpF with one glycerol per 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) is reconstructed
from time series of applied force and displacement
non-equilibrium analysis based on Langevin
equation
multiple trajectories can be combined to yield
statistically significant 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
from MD at 300K
from x-ray diffract. at 100K
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Bipolar orientation and diffusion of water
through GlpF
orientation
diffusion
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Filtering mechanism in GlpF
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water pair correlation
Correlated water dynamics in the channel
correlated displacement of waters in channel
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Aquaporin seeing waters in motion
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Pressure-induced water conduction in GlpF
p0
pgt0
plt0
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Pressure-induced water conduction in GlpF