Crystallography is unable to solve a large percentage
of protein structures anytime soon.
Structural genomics is an initiative to solve a large
There are 9 NIH-funded structural genomics centers/consortia in the USA, plus
commercial efforts and centers in other countries, for a total of >20
- Identify sequence families for which no empirical template
exists for homology modeling.
- Choose some members of each family as "targets".
- The Protein Data Bank maintains a
- In February, 2004, nearly 50,000 targets
were registered (75% in the previous year: Graph).
- Solve a target from each family by high-throughput crystallography,
providing a new template.
- This is the
- Infer function from similar structures of known function, to be
confirmed biochemically (Zhang & Kim).
- Homology model all members of each family, using the new templates.
By one estimate (Vitkup et al.), obtaining templates for 90% of proteins would
16,000 new sequence-unrelated structures. This is about three
times the world output of crystallography to date.
About 3% of this goal has been attained.
Eric Martz, University of Massachusetts, July 2003 (updated February 2004)
Protein Data Bank's Structural Genomics Page
- Success rates in crystallography.
efforts in structural genomics, Stevens, Yokoyama & Wilson,
Science 294:89, 2001.
Completeness in structural genomics, Vitkup, Melamud, Moult & Sander,
Nature Structural Biology 8:559, 2001.
Structural genomics takes off, Thornton,
Trends Biochem. Sci., 26:88, 2001.
genomics. Tapping DNA for structures produces a trickle,
Service, Science 298:948, 2002.
genomics: current progress, Gerstein et al.,
Science 299:1663, 2003.
The authors make the point that overall
progress is much larger than the number of solved structures, since each
solution serves as a template for homology modeling a large family of
sequences. Also, work is often stopped on a target when a sequence-related
target is solved; hence not all uncompleted targets are "failures".
of structural genomics: from structure to function,
Zhang & Kim, Curr. Opin. Chem. Biol. 7:28, 2003.
"These new structures have revealed many unexpected functional and
evolution relationships that were hidden at the sequence level."