Published June 28, 2004; Category: ARTS &
SCIENCES
Handling loads of protein data and speeding up expensive
experiments are key parts of computer scientists' work
The field of structural genomics - the study of the
three-dimensional geometric structures of proteins - is complicated
by vast amounts of data, expensive experiments and cumbersome
methods of analysis.
Computer Science Professor Bruce Randall Donald
and his students are working to ease this burden by developing
techniques that simultaneously minimize the number of experiments
and accelerate the data analysis involved in determining the
structure of proteins.
Bruce
Randall Donald
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Published in consecutive months of the Journal of Biomolecular
NMR (nuclear magnetic resonance), Donald, a graduate student and a
post-doctoral fellow present new algorithms that interpret NMR data
to reveal a protein's shape and molecular architecture. NMR surveys
a protein's molecular structure and uses tiny, spectroscopic
protractors and rulers to generate a network of geometric
measurements.
Learning about protein structure is especially relevant for
treating illnesses that alter protein function, such as cancer.
"In these papers, we discuss a new framework for thinking about
how to solve these problems, and our algorithms are highly
accurate," says Donald, the Joan P. and Edward J. Foley Jr. 1933
Professor of Computer Science and Adjunct Professor of Chemistry and
of Biological Sciences.
The first paper, published in June, explains the work of Christopher
Langmead, a doctoral student in Donald's laboratory who is now
Assistant Professor of Computer Science at Carnegie Mellon
University. Langmead's algorithm introduced new techniques for
assigning NMR measurements to specific molecular bonds. Most NMR
experiments measure a protein, reporting distances between molecules
and angles of chemical bonds, but the data doesn't indicate which
atoms or bonds the measurements correspond to.
"It's a little like taking all the heights and weights of
everyone at a cocktail party, but you don't know which height goes
with which person," Donald says.
Langmead's and Donald's technique assigns the measurements to the
correct nuclei, which helps to unveil the architecture of the
protein.
A second paper by Donald and Lincong Wang, a Dartmouth
post-doctoral fellow, will be published in July.
Lincong Wang
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This paper describes a new protein structure determination
algorithm, which solves complex algebraic equations that relate the
experimental data to the protein's geometry.
"Our algorithm requires less data and yet the resulting protein
structures are incredibly accurate," Donald says.
Unlike previous techniques, Wang's equations can be solved
exactly in a manner similar to solving the quadratic equation of
high school algebra fame. Wang and Donald say they hope their work
proves helpful to both structural genomics researchers as well as to
those in the broader structural biology field.
Research in Donald's laboratory is supported by the National Institutes of Health and the
National Science Foundation.
By SUSAN KNAPP
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