1. Functions of Aquaporins in mammals

2. Kidney Cortex Nephron proximal tubules collecting duct Aqp0 urine concentration reabsorption of water into blood The role of Aquaporins in the kidney

3. The role of Aquaporins in the kidney tetramers monomers

4. Glycerol Channel and the Aquaporin Family water transport in cells: aquaporins water+glycerol transport: aquaglycoporins ions and charged solutes excluded from transport tetrameric architecture

5. 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

6. Note the curved adjustment between lipids and protein

8. Competition of water and glycerol for H-bonds

9. 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

10. Steered MD simulation of glycerol passage through GlpF

11. 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!

12. Constructing the potential of mean force

13. Potential of mean force along channel axis attractive extra- cellular vestibule

14. Simulated system 3: GlpF with only water

15. GlpF crystallography without glycerol

16. Water arrangement in GlpF from x-ray diffract. at 100K from MD at 300K

18. orientation diffusion Bipolar orientation and diffusion of water through GlpF

19. Filtering mechanism in GlpF

20. Correlated water dynamics in the channel correlated displacement of waters in channel water pair correlation

21. Aquaporin: seeing waters in motion

22. p=0p>0 p<0 Pressure-induced water conduction in GlpF