Structural genomics: A pipeline for providing structures for the biologist

• Published in: Protein science Vol. 11; no. 4; pp. 723 - 738
• Main Authors: Chance, Mark R., Bresnick, Anne R., Burley, Stephen K., Jiang, Jian‐Sheng, Lima, Christopher D., Sali, Andrej, Almo, Steven C., Bonanno, Jeffrey B., Buglino, John A., Boulton, Simon, Chen, Hua, Eswar, Narayanan, He, Guoshun, Huang, Raymond, Ilyin, Valentin, McMahan, Linda, Pieper, Ursula, Ray, Soumya, Vidal, Marc, Wang, Li Kai
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.04.2002
• Subjects: Amino Acid Sequence; Animals; Bacterial Proteins - chemistry; Caenorhabditis elegans; Computational Biology - trends; Databases as Topic; Escherichia coli; Evolution, Molecular; Gene Order; Genomics - methods; Humans; Invited; ModBase; Models, Molecular; Molecular Sequence Data; Protein Structure, Tertiary; Proteins - chemistry; Proteins - physiology; Proteome - chemistry; Sequence Homology, Amino Acid
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.4570102

Progress in understanding the organization and sequences of genes in model organisms and humans is rapidly accelerating. Although genome sequences from prokaryotes have been available for some time, only recently have the genome sequences of several eukaryotic organisms been reported, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and humans. A logical continuation of this line of scientific inquiry is to understand the structure and function of all genes in simple and complex organisms, including the pathways leading to the organization and biochemical function of macromolecular assemblies, organelles, cells, organs, and whole life forms. Such investigations have been variously called integrative or systems biology and -omics or high-throughput biology. These studies have blossomed because of advances in technologies that allow highly parallel examination of multiple genes and gene products as well as a vision of biology that is not purely reductionist. Although a unified understanding of biological organisms is still far in the future, new high-throughput biological approaches are having a drastic impact on the scientific mainstream. The progress of the NYSGRC after its first year of funding from the NIH indicates that cautious optimism about the overall progress of the structural genomics initiatives is warranted. As of August 31, 2001, the NYSGRC completed 27 X-ray structures that resulted from the examination of more than 500 independent constructs expressed in E. coli. Comparative protein structure modeling with these 27 experimentally determined structures produced additional structural information for thousands of protein sequences. These models are publicly available via ModBase (http://guitar.rockefeller.edu/modbase). With the results of quantitative structure-structure comparisons and homology modeling, we can subdivide our structures into the four categories.