functions of aquaporins in mammals
Post on 08-Feb-2016
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Functions of Aquaporinsin mammals
Kidney Cortex
Nephron
proximal tubules collecting duct
Aqp0Aqp0 urine concentration
reabsorption of water into blood
The role of Aquaporins in the kidney
The role of Aquaporins in the kidney
tetramers
monomers
Glycerol Channel and the Aquaporin Family
water transport in cells: aquaporins
water+glycerol transport:aquaglycoporins
ions and charged solutes excludedfrom transport
tetrameric architecture
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
Note the curved adjustment between lipids and protein
Competition of water and glycerol for H-bonds
Simulated System 2:
GlpF with one glycerolper channel: initial state
GlpF with one glycerolper channel: after 1ns
entire conduction event needs to be enforced
Steered MD simulation of glycerol passage through GlpF
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!
Constructing the potential of mean force
Potential of mean force along channel axis
attractive extra-cellular vestibule
Simulated system 3: GlpF with only water
GlpF crystallography without glycerol
Water arrangement in GlpF
fromx-raydiffract.
at 100K
from MD
at 300K
orientation
diffusion
Bipolar orientation and diffusion of water through GlpF
Filtering mechanism in GlpF
Correlatedwater dynamicsin the channel
correlated displacementof waters in channel
water pair correlation
Aquaporin: seeing waters in motion
p=0 p>0 p<0
Pressure-induced water conduction in GlpF
Pressure-induced water conduction in GlpF
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