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