Functions of Aquaporins

in mammals
 Nephron
The role of
Aquaporins
in the kidney
Kidney
Cortex

proximal tubules collecting duct

Aqp0 urine concentration

Aqp0
reabsorption of water into blood
 The role of
Aquaporins
in the kidney

monomers

tetramers
 Glycerol Channel and the Aquaporin Family

water transport in cells: aquaporins

water+glycerol transport:
aquaglycoporins

ions and charged solutes excluded

from transport

tetrameric architecture
 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
Note the curved adjustment between lipids and protein
Competition of water and glycerol for H-bonds
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
Steered MD simulation of glycerol passage through GlpF
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!
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

from from MD
x-ray
diffract.
at 300K
at 100K
Bipolar orientation and diffusion of water through GlpF

orientation

diffusion
Filtering mechanism in GlpF
 water pair correlation Correlated
water dynamics
in the channel

correlated displacement
of waters in channel
Aquaporin: seeing waters in motion
 Pressure-induced water conduction in GlpF

p=0 p>0 p<0

Pressure-induced water conduction in GlpF