Transcript Slide 1
Functions of Aquaporins in mammals Nephron Kidney Cortex proximal tubules Aqp0 The role of Aquaporins in the kidney Aqp0 collecting duct urine concentration 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 extracellular vestibule Simulated system 3: GlpF with only water GlpF crystallography without glycerol Water arrangement in GlpF from x-ray diffract. at 100K from MD at 300K Bipolar orientation and diffusion of water through GlpF orientation diffusion Filtering mechanism in GlpF water pair correlation correlated displacement of waters in channel Correlated water dynamics in the channel Aquaporin: seeing waters in motion Pressure-induced water conduction in GlpF p=0 p>0 p<0 Pressure-induced water conduction in GlpF