Water Channels in Cell Membranes - Movie Explanation

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 (see figures in the web site
below).  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 Pittsburgh NSF Supercomputer Center was
instrumental for the accomplishment of 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 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 at http://www.ks.uiuc.edu/Research/aquaporins).  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 the
Science magazine (Tajkhorshid et al., Science Apr 2002, 296:525).

This work was performed by the Theoretical and Computational
Biophysics group, the 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 at http://www.ks.uiuc.edu/Research/aquaporins or contact 
Dr. Emad Tajkhorshid (217-244-6914; emad@ks.uiuc.edu).

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