University at Buffalo scientists working in the field of
protein-structure determination have been awarded a $2 million
Information Technology Research grant by the National Science
Foundation.
The UB project is designed to use new technologies such as Grid
computing, data mining and collaborative environments to enhance
protein-structure determination, a key tool in the rational drug-design
process, which bases the discovery of new pharmaceuticals on precise
knowledge of protein structures.
The Buffalo team is affiliated with the Strategically Targeted Academic
Research (STAR) Center in Disease Modeling and Therapy Discovery at UB,
sponsored by the New York State Office of Science, Technology and
Academic Research.
The funding will enable the development of new software for
crystallographers to tap computational and scientific power to enhance
SnB, the widely used protein-structure determination software developed
by scientists at UB and Hauptman-Woodward Medical Research Institute
(HWI) in Buffalo.
When it became publicly available in 1995, SnB represented a quantum
leap in structure determination, allowing researchers to solve
structures with virtually no input from the user, UB said. Last year,
the formula on which it was based, developed by Nobel Laureate Herbert
Hauptman, president of HWI, was designated one of the top 10 algorithms
of the 20th century by Computing in Science & Engineering magazine.
Through refinements and new editions of the software developed by UB and
HWI researchers, this "black box" approach now is capable of solving the
structures of molecules of thousands of non-hydrogen atoms, UB said. It
also can solve critical substructures that allow for the determination
of proteins with tens of thousands of atoms, which only a few years ago
would have been regarded as impossible.
As emerging research in the fields of genomics and proteomics has shown,
unraveling the structures of larger, complex proteins that may be
important targets for new pharmaceuticals requires even more from
SnB.
"SnB has had an enormous impact on the crystallographic community," said
Russ Miller, UB Distinguished Professor in the Department of Computer
Science and Engineering, principal investigator and director of UB's
Center for Computational Research (CCR). "But its ultimate potential is
unknown. This grant will allow us to make advances in structure
determination by exploiting new computational paradigms."
One of those new paradigms, Miller said, is the computational Grid, a
state-of-the-art platform in which hundreds, even thousands, of
computers from across the nation and the world can be tapped to solve a
single problem. Grid computing, he said, harnesses not just the
machines' computing power, but also storage, device and personnel
resources so they behave as a single environment.
"Creating a Grid-enabled version of SnB puts us in a position to really
tackle larger structures and at the same time create collaborative
environments between users of programs who can benefit from each other's
expertise without working together in a traditional sense," Miller
said.
The project will also enable Miller and colleagues to take advantage of
new techniques in data mining, allowing a software agent to sift through
enormous amounts of data that are deposited in an SnB data warehouse at
CCR and identify critical patterns that can lead to more efficient
structure determinations.
"Once the data are in the repository, the software agent will
continually mine them in an effort to determine adjustments in parameter
settings, so the next time someone uses the package to solve a structure
with characteristics similar to those in the warehouse, SnB will be even
more efficient," he said. "Essentially, it will be able to improve
itself."
Once the software has been written that creates the appropriate
collaborative and data-mining environments, the UB and HWI developers
will begin to create a virtual community.
To create the Grid-enabled version of SnB, CCR staff are harnessing key
resources, including a Dell server cluster that is one of the world's
largest commodity-based clusters and a Pentium4 Dell cluster with
Myrinet interconnectivity that is one of the most powerful machines in
the world, as well as other machines from SGI, IBM and Sun.
Using a FakeSpace ImmersaDesk powered by SGI Onyx 2 and SGI 3300W
visualization systems, CCR's visualization scientists are producing a
collaborative environment that will allow SnB users around the globe to
visually work together on structures.
In addition to Miller, investigators on the grant are Josephine Anstey,
assistant professor of media study at UB who works on collaborative
environments; Charles Weeks, senior research scientist at HWI and UB
professor of structural biology, who originally developed SnB with
Miller and Hauptman; and Aidong Zhang, UB professor of computer science
and engineering, who studies and develops techniques for data mining.
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