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Just four years ago, the world got
its first view of what a potassium channel looks like.
An X-ray crystallographic image taken in 1998 by Rod
MacKinnon and collaborators at Rockefeller University
revealed the channel's three-dimensional form. Its mouth
was perfectly sized to admit a potassium ion stripped
of its surrounding cloud of water molecules but would
not let in a dehydrated sodium ion. The channel was
long enough to hold several ions at once, suggesting
how it could transport ions so quickly. And the channel's
negatively charged interior, which resembled the environment
of water, suggested it could entice a potassium ion
to shed its water molecules and slip inside as easily
as if it remained in solution. That, however, was where
the insights ended.
"The X-ray images gave us the
essential elements that are needed to understand the
channel's operation. But these are static, so one cannot
see the forces that come into play when the ions and
the water molecules are moving," Roux says. To
understand how the channel ushers potassium ions along,
and why the ions don't repel one another more strongly,
scientists needed to create and animate a virtual version
of the entire system using molecular dynamics. This
was done using supercomputers, including the SGI Origin2000
at NCSA at the University of Illinois at Urbana-Champaign.
Berneche and Roux used a program known
as CHARMM (Chemistry at Harvard Molecular Mechanics),
which is designed specifically to run molecular dynamics
simulations, to build a potassium channel, cell membrane
molecules, water molecules and potassium ions. "Our
calculations are a way to exploit the fantastic information
obtained recently from the X-ray images so that we can
really connect them to the most fundamental physical
laws," Roux says. All in all, the program tracked
the activities of about 40,000 atoms--a hefty computational
burden.
But even with today's most powerful
supercomputers, it would be impossible to track the
movements of every atom in the system while simulating
a single potassium ion arriving at, entering, and completely
traversing the channel. So Berneche and Roux adopted
a more practical strategy and mapped the energetic topography
of the journey instead. The technique can be likened
to measuring the hills and valleys a rolling ball might
encounter. The places within the channel where repulsive
atomic forces encourage ions to roll away would be the
hills. Sites within the channel where energy barriers
are low tend to slow the travel of ions like valleys.
With this topography mapped out, they were able to calculate
the average energetic environment a traveling potassium
ion would be likely to see. 
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