Supercomputer Maps One Million Atoms of a Complete Virus in First
Simulation of a Life Form
Virtual virus takes 100 days on supercomputer, 35 years on a desktop
March 23, 2006
For the first time, researchers have visualized the changing atomic structure of a
virus by calculating how each of the virus' one million atoms interacted with each
other every femtosecond--or one-millionth-of-a-billionth of a second. A better
understanding of viral structures and mechanisms may one day allow
researchers to design improved strategies to combat viral infections in plants,
animals and even humans.
Led by Klaus Schulten at the University of Illinois at Urbana-Champaign, the
team tapped the high-performance power of the National Center for
Supercomputing Applications (NCSA) processors to accomplish the task. Still, it
took about 100 days to generate just 50 nanoseconds of virus activity. Schulten
says it would have taken the average desktop computer 35 years to come up
with the results.
The simulation revealed key physical properties of satellite tobacco mosaic virus,
a very simple, plant-infecting virus. Ultimately, scientists will generate longer
simulations from bigger biological entities, but to do so, they need the next
generation of supercomputers, the so-called "petascale high-performance
computing systems." The National Science Foundation (NSF) is currently
devising a national strategy for petascale computing to give scientists and
engineers the resources needed to tackle their most computationally intensive
research problems.
NSF supported the work through funding to the NCSA and through a graduate
research fellowship to study first-author Peter Freddolino. The National Institutes
of Health also provided support for the study, which was published in the March
issue of Structure
Researchers simulate complete structure of virus–on compute
Jim Barlow, Life Sciences Editor
217-333-5802; jebarlow@uiuc.edu
CHAMPAIGN, Ill. — When Boeing and Airbus developed their latest aircraft, the
companies’ engineers designed and tested them on a computer long before the
planes were built. Biologists are catching on. They’ve just completed the first
computer simulation of an entire life form – a virus.
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 sub-viral 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 that 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.
The necessary calculation was done at 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.
“It's a simple little virus -- so simple that biologists often refer to it as a "particle"
rather than organism, so small and primitive that it can only proliferate in a cell
that's already been hijacked by another virus. But a recent simulation of the
satellite tobacco mosaic virus is also a striking first. There's never been a
computer simulation of an entire life form at atomic detail. Until now.
A report on the work by Klaus Schulten and his collaborators at the University of
Illinois at Urbana-Champaign and the University of California at Irvine appears in
the March edition of Structure. It relied on the shared-memory SGI Altix
supercomputer at the National Center for Supercomputing Applications (NCSA),
home to the largest open academic computing environment in the country.
"The ideal situation is to work with a powerful computing platform that provides
output quickly and with minimal disturbance. In this way, the underlying science
is the focus of the effort. NCSA provided exactly that. NCSA has always provided
that," says Schulten, a long-time user.
"The federal government is renewing its commitment to high-performance
computing through a series of major upcoming awards for systems substantially
larger than those we support today. It's incumbent upon centers like NCSA to
make the most of these investments by working closely with scientists like Prof.
Schulten as well as entire communities of scientists. We have developed new
ways to allocate supercomputing resources to give scientists what they need in
order to make incredible breakthroughs like the simulation of an entire living
thing," says Thom Dunning, NCSA's director.
Previously, all-atom molecular dynamics simulations on such a large structure
have been infeasible. As a result, researchers often look at only part of a
symmetric virus and use symmetric boundary conditions. Or they might simulate
smaller portions of the virus or simulate the entire virus at a much coarser
resolution.
The simulations of the satellite tobacco mosaic virus involved as many as one
million atoms and simulation times of more than 50 nanoseconds. This required
massive amounts of computing time -- 35 processor years. And it required a
modern, scalable molecular dynamics code -- NAMD, which Schulten and his
team have been developing for years.
"This is on the highest end of what is feasible today," says Schulten. "The
approach is something that we learned from engineers: Reverse engineer the
subjects you're interested in and test fly them in the computer to see if they work
in silico the way they do in vivo. Naturally, deeper understanding of the
mechanistic properties of other, more complicated viruses will eventually
contribute to public health and medicine."
The simulations allow the research team to compare the behavior of the full virus
and will help scientists determine what factors are important to the virus'
structural integrity and how those factors might influence assembly of the virus
inside host cells.”
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
The computer simulations were carried out in Schulten’s Theoretical and
Biophysics Group’s lab at the Beckman Institute for Avanced Science and
Technology.
Other co-authors were Anton Arkhipov, a doctoral student in physics at Illinois,
and 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 NCSA 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.