Water Channels in Cell Membranes
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The movie shows the motion of water through a membrane water channel, aquaporin. Aquaporins are proteins instrumental for the flow of water across the boundaries of a variety of cells, ranging from bacterial and plant cells to those in many organs in the human body. Due to the fatty nature of the cell membrane, water cannot efficiently be exchanged between the interior of the cell and outside. These channels were, therefore, devised in cells that either have to handle large volumes of water flow, or need to provide a fast mechanism of water adjustment. In humans, these channels are distributed, for example, in kidneys where they mediate reabsorption of about 200 liters of water from urine back to blood every day. They are also present in the eye, brain, blood cells, etc, and their impaired function has been related to such diseases like diabetes insipidus or congenital cataracts.

In the movie, we are looking at the channel from the side, i.e., from inside the membrane, watching the transmembrane flow of water through the channel. One half of the channel, which is between us and water, has been made transparent to visualize the interior of the channel where the water flows. The other half of the channel, in the back of flowing water, is shown using a "surface" representation of the protein. The white parts are nonpolar, red and blue colors indicate negatively and positively charged parts, respectively. One recognizes that the pore region of the channel is composed mainly of nonpolar parts (white), except for the narrowest section of the channel, located in the upper half, which is marked by a major positive charge (shown in blue). This part of the channel is the actual filter that prevents the entrance of larger molecules. The single file of water inside the channel connects the bulk water on the two sides of the membrane, which are otherwise completely isolated by the fatty lipids of the membrane. Water (H2O) molecules are colored using red (for O - oxygen) and white (for H - hydrogen). One of the water molecules is colored yellow to make it easier to follow its motion through the channel.

The animation is made from a multinanosecond molecular dynamics simulation of a system composed of 106,000 atoms. It is one of the largest system ever simulated on this time scale. The simulated system included an aquaporin tetramer, which is the natural form of the channel, embedded in a patch of lipid bilayer membrane and hydrated by slabs of water on both sides. This setup provides the most faithful description of the channel in its natural environment. Full atomic description of all composing elements resulted in a system of 106,000 atoms. The simulations were computationally extremely demanding, and the use of supercomputer time on the National Science Foundation's (NSF) Pittsburgh Supercomputing Center was instrumental for accomplishing the project.

Although computationally expensive, the careful setup of the system and the length of the simulation allowed us to completely describe the permeation of water through the channel, as driven by thermal motions of atoms, in real time (see the movie). In other words, this simulation presents one of the first examples in which a biological event (transmembrane permeation of materials across the membrane) is simulated naturally in full detail.

The results are in excellent agreement with the crystallographically observed properties of the channel and published jointly by computational and biomedical (UCSF) researchers in one of the April issues of the Science magazine. The calculations though, went beyond the experimentally accessible boundaries, revealing the orientation of water molecules as they travel inside the channel, a property that cannot be determined experimentally, since hydrogen atoms could not be observed by x-ray crystallography. By monitoring water, we discovered a peculiar arrangement (a wing-shaped or bipolar configuration) inside the channel (please see the small movie available here). The travel of water can be described as a dance, in which the dancer is forced to turn 180 degrees in the middle of the stage. Based on this observation, we proposed a new mechanism of proton preclusion (proton blocking) that solved a long lasting puzzle regarding the biological function of aquaporins: how they manage to allow water to pass, but not the smaller protons. This new mechanism has been published in Science magazine (Tajkhorshid et al., Science Apr 2002, 296:525).

This work was performed by the Theoretical and Computational Biophysics Group, the National Institutes of Health (NIH) Resource for Macromolecular Modeling and Bioinformatics, at the Beckman Institute, University of Illinois at Urbana-Champaign and supported by the NIH and NSF.

For further details and more figures, please visit our "aquaporin" research page or contact Dr. Emad Tajkhorshid (217-244-6914; emad@ks.uiuc.edu).

Text file of explanation available here. A .mpeg version of the movie is available here (13.1 MB).