Transcript
Page 1: Functions of Aquaporins in mammals

Functions of Aquaporinsin mammals

Page 2: Functions of Aquaporins in mammals

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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Page 8: Functions of Aquaporins in mammals

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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Page 18: Functions of Aquaporins in mammals

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


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