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In their quest
to study life, biologists apply engineering knowledge somewhat
differently: They reverse-engineer life forms, test fly them in the
computer, and see if they work in silico the way they do in vivo.
This technique previously had been employed for small pieces of
living cells, such as proteins, but not for an entire life form
until now. The accomplishment, performed by computational
biologists at the University of Illinois at Urbana-Champaign and
crystallographers at the University of California at Irvine, is
detailed in the March issue of the journal Structure.
Deeper understanding of the mechanistic properties of viruses,
the researchers say, could not only contribute to improvements in
public health, but also in the creation of artificial nanomachines
made of capsids -- a small protein shell that contains a viral
building plan, a genome, in the form of DNA or RNA.
Viruses are incredibly tiny and extremely primitive life forms
that cause myriad diseases. Biologists often refer to them as
particles rather than organisms. Viruses hijack a biological cell
and make it produce many new viruses from a single original. They've
evolved elaborate mechanisms of cell infection, proliferation and
departure from the host when it bursts from viral overcrowding.
For their first attempt to reverse-engineer a life form in a
computer program, computational biologists selected the satellite
tobacco mosaic virus because of its simplicity and small size.
The satellite virus they chose is a spherical RNA subviral agent
that is so small and simple that it can only proliferate in a cell
already hijacked by a helper virus -- in this case the tobacco
mosaic virus, which is a serious threat to tomato plants.
A computer program was used to reverse-engineer the dynamics of
all atoms making up the virus and a small drop of salt water
surrounding it. The virus and water contain more than a million
atoms altogether.
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 The necessary calculation was done at the University of Illinois
on one of the world's largest and fastest computers, operated by the
National Center for
Supercomputing Applications. The computer simulations provided
an unprecedented view into the dynamics of the virus.
"The simulations followed the life of the satellite tobacco
mosaic virus, but only for a very brief time," said co-author Peter
Freddolino, a doctoral student in
biophysics and
computational biology at Illinois. "Nevertheless, they
elucidated the key physical properties of the viral particle as well
as providing crucial information on its assembly."
It may take still a long time to simulate a dog wagging its tail
in the computer, said co-author Klaus Schulten, Swanlund Professor
of Physics at Illinois. "But a big first step has been taken to
‘test fly' living organisms," he said. "Naturally, this step will
assist modern medicine as we continue to learn more about how
viruses live."
The computer simulations were carried out in Schulten's
Theoretical and Biophysics Group's lab at the
Beckman Institute for
Advanced Science and Technology.
Other co-authors were Anton Arkhipov, a doctoral student in
physics at Illinois,
along with Alexander McPherson, a professor of molecular biology and
biochemistry, and research specialist Steven Larson, both at UC-Irvine.
The work was supported by the National Institutes of Health and
by computing time from the National Center for Supercomputing
Applications through its National Science Foundation funding.
The Beckman Institute is an interdisciplinary research institute
devoted to basic research in the physical sciences, computation,
engineering, and biological, behavioral and cognitive sciences.
[Jim Barlow, life sciences editor,
University
of Illinois at Urbana-Champaign news bureau] |
