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Protein Showers: 5¢
How proteins open and close has long been a mystery that will soon be
unlocked for use. It seems proteins like to take showers and dry off
according to matching research correlated from Tennessee to California.
This is a biggie and mother nature is watching.
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Secrets of Protein Folding Coming Unlocked
18 September 2007 - sciencedaily.com
A team led by biophysicist Jeremy Smith of the
University of Tennessee and Oak Ridge National Laboratory (ORNL) has
taken a significant step toward unraveling the mystery of how proteins
fold into unique, three-dimensional shapes.
Using ORNL's Cray XT4 Jaguar supercomputer as well as computer systems
in Italy and Germany, the team revealed a driving force behind protein
folding involving the way its constituents interact with water. The
team's results are being published in this week's edition of the
Proceedings of the National Academy of Sciences.
Proteins are the workhorses of the body, taking on a wide variety of
tasks. They fight infections, turn food into energy, copy DNA and
catalyze chemical reactions. Insulin is a protein, as are antibodies
and many hormones.
Scientists are still very interested in deciphering how proteins work.
A protein is a string of amino acids, and what it does is determined
by the shape it takes. That shape is determined by the sequence of the
amino acids. Like a piece of biological origami, the protein folds
itself into the form necessary to carry out its job. Without the shape
the protein would be worthless.
"Understanding the mechanism by which proteins fold up into unique
three-dimensional architectures is a holy grail in molecular
biology," explained Smith, who holds the first UT-ORNL Governor's
Chair and is a member of the Biochemistry and Molecular Biology
Department at UT.
"Unfortunately, if you give me the sequence of amino acid building
blocks in the protein, I cannot tell you what the structure would be,"
he said. "If I had been able to do that with a computer a while ago,
the work behind about a dozen Nobel prizes -- those awarded for
experimental work on protein structure determination -- would not have
been necessary."
Working on a smaller chain of amino acids known as a peptide, the
group showed that the folding is determined largely by how parts of
the peptide interact with water. Areas that shun water are said to be
hydrophobic, and the team's results show that the way water wets
these hydrophobic areas determines the ultimate shape and behavior
of the peptide.
In particular, the team determined that small hydrophobic areas of the
peptide, up to the size of a water molecule, induce different behavior
in water than larger hydrophobic areas, and that this difference is
crucial for the folding. This insight builds on the work of another
team, based at the University of California--Berkeley.
"David Chandler and his colleagues at Berkeley have a theory stating
that hydrophobicity is qualitatively different on different length
scales," Smith said. "If you have small hydrophobic molecules or
groups that are themselves roughly the size of a water molecule, the
water doesn't seem to be too bothered by these groups. But when you
get hydrophobic entities as long as several water molecules, the water
molecules have a problem with that. They can't cloak themselves around
the hydrophobic surface anymore, and there is a dewetting or drying
effect as they are repelled from the surface.
"Our simulations have shown that Chandler's theory works for peptides,
and, moreover, that the drying effect determines which structure
our peptide adopts. It's kind of 'dry it off then fold it up.'"
Smith said his team's achievement was made possible by
high-performance computing, noting that Jaguar is currently rated
the second most powerful computing system in the world. Smith also
said that his team will need increasingly powerful supercomputers for
additional simulation. While the team so
far has been able to simulate about a microsecond in the life of a
peptide, they must eventually be able to increase that time a
thousand-fold, to milliseconds, and simulate proteins that are 10 to
100 times as large as the peptides.
"The runs were a couple of microseconds, which was adequate for the
peptide that was simulated," Smith explained. "But the team is looking
forward to increased computing capacity as it moves forward. The
technique used is molecular dynamics simulation, and it needs
high-performance leadership supercomputing to reach the length and
timescales needed to fold a complete functional protein in the
computer. With the projected capability improvements in Jaguar over
the next couple of years, we will soon be approaching that goal."
Smith made it clear that the achievement would represent a
watershed in the field.
"When we do eventually find out how to calculate protein structure
from sequence," he said, "then a major revolution will come upon us,
as we will have the basis to move forward with understanding much of
biology and medicine, and the applications will range from rationally
designing drugs to fit clefts in protein
structures to engineering protein shapes
for useful functions in nanotechnology and bioenergy."
Note: This story has been adapted from a news release issued by
University of Tennessee at Knoxville.
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Messages From Earth |
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A synopsis of the first 5 hours in the series Planet Earth.
Read more
On the dark side of human nature.. [PDF]
Reasons
Logical Explanations
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