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| Hamburg/Amsterdam, 11 July 2006 |
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| Mapping the protein world
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| The inventors of ARP/wARP: Victor Lamzin [above] and Anastassis Perrakis [below]. |
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Press
Release 11 July 2006 [PDF]
A software package called ARP/wARP is helping to expose the hidden
world of biological molecules
In the early days of X-ray
crystallography obtaining a three-dimensional model of a protein
required wire models, screws, bolts and years of tedious calculations
by hand. Today macromolecular models are built by computers
– thanks to sophisticated software and in particular a package
called ARP/wARP. Developed by Victor Lamzin at the
Hamburg Outstation of the European Molecular Biology
Laboratory [EMBL] and Anastassis Perrakis at the Netherlands
Cancer Institute [NKI] in Amsterdam, ARP/wARP is currently
used by over 2,000 researchers throughout the world. The capabilities
of this software will now expand even further – thanks to a
grant of over 800,000 US Dollars from the U.S. National Institutes
of Health [NIH].
The grant, which will run over four years, comes at a perfect time.
"More than 1,000 research laboratories from over 50 countries
are holding ARP/wARP licenses and by June this year our paper
that described the key innovative feature of ARP/wARP in Nature
Structural Biology in 1999 has reached the magic number of 1,000
citations in the scientific literature. This has created an incredible
drive for further scientific development," Lamzin says. "The new
funding gives us a push to advance the software's ability to recognise
and distinguish different types of macromolecular objects,
for example DNA, and to improve the automated generation of
structural models. ARP/wARP has made the life of structural
biologists worldwide a lot easier and will do even more so once
the new features planned under the NIH grant have been implemented."
ARP/wARP transforms 'electron density maps', produced in
experiments that bombard protein crystals with X-rays, into 3-dimensional structures. "X-ray experiments result in 'diffraction
patterns' that can't be interpreted using our eyes," Lamzin says.
"These have to be reconstructed into a three-dimensional image
through mathematics and models. This was a very tedious, timeconsuming,
and subjective process."
ARP/wARP was the first, and for a while the only, software that
could generate models to fit experimental data automatically and
very accurately. It has cut down the time necessary to create structural
models from weeks to minutes.
This grant will allow the scientists to explore new concepts of
model-building and enlarge the scope of data that the software
can handle. ARP/wARP deals very well with high-resolution data
that allows to distinguish individual atoms, but much of the data
that scientists have to deal with is of lower quality. The software
has steadily been improved to work with lower-resolution data,
and Lamzin and Perrakis know how to stretch it even further.
"The high-throughput revolution in Structural Biology allows us
to work on more and more complex problems relevant to human
health," Perrakis says. "Knowing the structures of molecules that
play crucial roles in cancer, cardiovascular and neurodegenerative
diseases and molecules from pathogenic bacteria or viruses
will contribute to design new revolutionary therapeutic strategies."
To meet this objective, the scientists intend to study crystals of
proteins bound to diverse drug candidates or containing different
types of large molecules.
"ARP/wARP needs to meet a two fold challenge: firstly, it needs
to be able to work with structural information at lower resolution,
within the range of 3.0 to 3.5 Ångstroms, and secondly, the models
produced have to be complete and validated. The new NIH
grant will help us to approach these aims. In the future
researchers will be able to focus on structure analysis rather than
just building the structure and, who knows, by combining
ARP/wARP with new cell imaging techniques we might be able to
model the molecules of a complete cell," Perrakis concludes.
Press Contact
Anna-Lynn Wegener
Press Officer
EMBL Heidelberg
Tel: +49 +6221 387-8452
Email: wegener@embl.de
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