Download Protein Origami

Well matched MRI-like Nuclear Magnetic
Resonance (NMR) experiment (A)
and Rosetta computer-generated (B)
renditions of a protein’s structure. The
Rosetta software can generate a protein
structure, which could take several
months to experimentally determine, in a
few days and at a fraction of the cost.
Credit: Srivatsan Raman, Harvard
University
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Protein
Origami
David Baker,
Professor,
University of
Washington
A human-generated folded protein
from the online game Foldit. The idea
of the game is to find out if the patternrecognition and puzzle-solving abilities
of people make them more efficient than
existing computer programs at some
tasks involved in predicting protein
structure. Such strategies might then be
added to folding prediction software.
Credit: David Baker, University of
Washington
The automatic prediction of a known
protein structure (red) by the Robetta
server overlaid on the native structure
(blue). The agreement between both
structures shows the atomic-level
accuracy of Robetta’s predictions.
Credit: Srivatsan Raman, Harvard
University
TeraGrid resources assist in the field of protein structure
prediction, helping to decode illness and disease.
I
n the online game Foldit, human players, from high
school students to retirees, are manipulating protein
molecules as part of an effort to understand how
proteins pack themselves into various shapes to
perform the many functions they have in the body.
Meanwhile, TeraGrid computational resources, and a
TeraGrid Science Gateway called the Robetta Portal, are
making it possible for thousands of researchers to look
at the structures of thousands of proteins at once. These
resources are helping move the field toward accurately
predicting and designing protein structures and protein
complexes, eventually with specific functions or disease
targets in mind.
Protein molecules are the workhorses of cells in all
living things. They carry oxygen in the blood, break down
glucose in the body to release energy, capture sunlight to
feed growing plants, catalyze the chemical reaction that
makes fireflies glow, and a lot more.
Proteins also aid viruses in invading cells. AIDS can be
tied to proteins that break through cellular defenses and
replicate the HIV virus. Cancer is linked to damage in
proteins that inhibit uncontrolled cell growth. Alzheimer’s
disease is believed to be related to malfunctioning
proteins that are normally part of healthy brain cells.
The duties proteins perform or do not perform are
governed by the shapes into which the ribbon-like
chains of up to 1,000 amino acids, basic building blocks
of life, fold themselves. Protein folding should produce
a protein’s most stable, functional structure, with
some amino acids wrapped inside and others hanging
outside, some pairs of amino acids near each other,
others positioned far apart. “When proteins do not align
correctly, sickness and sometimes death can occur,” says
David Baker, a University of Washington biochemist.
Both Foldit and Robetta stem from the Rosetta software
developed by Professor Baker and colleagues. Rosetta is
software for predicting and designing protein structures,
and studying protein folding mechanisms and proteinprotein interactions. Robetta automates the prediction
process in a server environment, in effect putting it
online.
How does Robetta work? If a sequence has similarities
to a known protein structure, Robetta leverages that
in modeling the structure of the subject protein. If a
sequence does not resemble a known protein, the system
applies a storehouse of knowledge about proteins and
protein structure and builds a model of the subject
protein’s structure from the ground up.
Foldit also is rooted in Rosetta. The game is designed to
find out if the pattern-recognition and puzzle-solving of
people make them more efficient than existing computer
programs at some tasks involved in predicting protein
structure, strategies that might then be added to folding
prediction software. Determining the three-dimensional
shapes of proteins may ultimately lead to finding cures
for major human diseases by manipulating proteins,
or even designing new ones, to fight HIV, cancer,
Alzheimer’s, or malaria, for example.
The problem is computationally demanding, however.
“There are a huge number of possible structures that a
protein could have,” says Baker, who also is a Howard
Hughes Medical Institute scientific investigator. He
likened the task to searching a large planet full of hills
and valleys for the planet’s low point. “In that case, it
helps to have a lot of explorers in the field,” says Baker.
Currently serving nearly 8,000 registered users,
Robetta allows researchers worldwide to submit
protein sequences for automated structural analysis.
The TeraGrid spreads the work over a variety of
computing systems, including powerful supercomputers.
For instance, Robetta can now run up to 300 jobs
simultaneously in a distributed computing system of
nearly 30,000 processors that makes use of machines
at TeraGrid partner, Purdue University and on other
campuses. The Robetta project also has made use of
TeraGrid resources at the San Diego Supercomputer
Center and the National Center for Supercomputing
Applications at the University of Illinois.
In addition, the TeraGrid has made Robetta’s power more
accessible to researchers through the Robetta Portal
Science Gateway, a website that makes submission of
sample protein sequences for analysis easier. “It was just
a natural match,” says Nancy Wilkins-Diehr, TeraGrid
Area Director for Science Gateways. “The portal gives
everyone access to this very high-quality, award-winning
code.”
“Having access to the massive computing resources of
the TeraGrid is revolutionizing the approaches that are
open for protein structure prediction,” Baker says.
Relevant links:
Robetta Portal http://robetta.bakerlab.org/
Foldit http://fold.it/portal/
Purdue University: http://purdue.edu
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