Midwest Center for Structural Genomics: Filling the structural biology pipeline

ARGONNE, Ill. (Aug. 19, 2005) — Faster, easier-to-use X-ray beamlines, such as those operated by the new GM/CA CAT, are allowing researchers to increase the pace of determining atomic structures of biomolecules important to life. This structural information will help reveal the roles that proteins play in health and disease and lead to structure-based medicines and therapies to treat genetic and infectious diseases.

GM/CA Director Janet Smith credits the Protein Structure Initiative (PSI) funded by the National Institute of General Medical Sciences as a key motivator to build faster, more automated beamlines. The PSI is a 10-year, $600 million program to reduce the costs and cut the time needed to determine a three-dimensional protein structure. The first step is to determine the 3-D structures of hundreds of unique proteins and then be able to determine the structures of others based on a library of structures and their corresponding DNA sequences.

Argonne structural biologists are anxious to begin using the new beamlines to continue their race to solve proteins and biomolecular structures. Argonne is home to one of the PSI's major centers – the Midwest Center for Structural Genomics (MCSG). Researchers have been using Argonne-managed beamlines at the Advanced Photon Source, but beamline research time is limited.

The PSI funded MCSG as a pilot center in 2000 to slash the average cost — from $300,000 to $50,000 — and time — from months and years to weeks and days — to analyze a protein structure.

The MCSG developed innovative, robotic approaches to streamline the multiple, complex steps of generating protein structures. “In fiscal year 2000,” said MCSG Director Andzrej Joachimiak, “ Argonne 's MCSG solved 15 protein structures for an average cost of $306,000 each. By the end of PSI in 2005, 120 structures were determined for an average cost of $66,000.”

PSI2, the second phase, which was announced in 2005, shifts the focus to producing thousands of protein structures that will be used to determine many more structures with computer modeling. PSI2 named the MCSG one of its four large-scale centers and granted MCSG $52.7 million over the next five years.

In fiscal year 2006, the MCSG plans to determine 150 structures for an average of $60,000 each. The structures are contributed to the Protein Data Bank to be shared and used by the biology community.

The MCSG has worked with manufacturers to create robots to speed the arduous process of creating a protein crystal to be studied in a beamline.

The following chart illustrates gains in MCGS productivity between 2001 and 2005:

— Evelyn Brown

For more information, please contact Steve McGregor (630/252-5580 or media@anl.gov) at Argonne.