BioCentury
ARTICLE | Tools & Techniques

Structural genomics

November 20, 2000 8:00 AM UTC

Over the last five years, structure-based drug design has fallen out of favor because protein structure determination was too slow and expensive. In its place, high throughput screening has come into vogue as a drug discovery tool in the belief that it would be superior to structure-based approaches. But new structural genomics initiatives promise to bring structure-based design back to the forefront with the structures of large numbers of new targets available either in the public domain or for sale.

Structure determination has been slow, taking two years and more than $100,000 per structure. Besides the time and cost, the available structures have been limited to the few proteins that have been amenable to either X-ray diffraction or nuclear magnetic resonance (NMR) analysis. Indeed, the Protein Data Bank (PDB), a public archive of biomolecular structure information supported by the National Science Foundation, the Department of Energy and the NIH, contains about 340 unique protein folds or topologies represented by about 12,000 different proteins, minuscule in comparison to the number of available gene sequences. ...