SCIENCE AT THE EDGE SEMINAR

Friday, 22 April 2011 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:15

Speaker: Carol L. Farr
         Joint Center for Structural Genomics & Department of Molecular Biology,
         The Scripps Research Institute, La Jolla, CA

Title:   Structured Salvage of Failed Pfam Families from the Protein Structure
         Initiative: Strategy, Struggles and Successes


Abstract:

With the completion of sequencing of the genomes of human and other organisms,
attention has focused on the characterization and function of proteins, the
products of genes.  The availability of enormous amounts of sequence data and
the growing impact of structural biology on biomedical research have prompted
scientific groups from several countries to undertake projects in the emerging
field of structural genomics. The objective is to make these structures widely
available for clinical and basic studies that will expand the knowledge of the
role of proteins both in normal biological processes and in disease.  The
National Institute of General Medical Sciences (NIGMS) has played a major role
in this, establishing in 1999 a national program entitled the Protein Structure 
Initiative.

Target selection for the NIGMS Protein Structure Initiative phase 2 (PSI-2)
focused extensively on large protein families primarily based on Pfam protein
domains (http://pfam.sanger.ac.uk/).  Many potential protein targets are found
within these large families and a typical structural genomics strategy is to
select multiple representatives of these families to process in parallel. These
multiple opportunities allow attrition at the specific protein level, while
maintaining a high success rate at the family level.  The consortium at the
Joint Center for Structural Genomics (www.JCSG.org) has a structure pipeline
that has been designed to ensure high success rates that account for high
attrition, but it is important to analyze individual failed targets to determine
if salvage efforts can be beneficial, especially in light of the increasing
difficulty of targets in the next phase PSI: Biology.  Here we present a summary
of the overall Protein Strucutre Initiative strategy, the structure salvage
strategy, as well as the challenges and successes of the use of these salvage
methods to increase the number of solved targets and extend Pfam family coverage. 
The JCSG is supported by NIH, National Institute of General Medical Sciences,
Protein Structure Initiative grants U54 GM094586 and U54 GM074898.