title: The structural genomics experimental pipeline: insights from global target lists.
abstract: Structural genomics (SG) initiatives are currently attempting to achieve the high-throughput determination of protein structures on a genome-wide scale. Here we analyze the SG target data that have been publicly released over a period of 16 months to assess the potential of the SG initiatives. We use statistical techniques most commonly applied in epidemiology to describe the dynamics of targets through the experimental SG pipeline. There is no clear bottleneck among the key stages of cloning, expression, purification and crystallization. An SG target will progress through each of these steps with a probability of approximately 45%. Around 80% of targets with diffraction data will yield a crystal structure, and 20% of targets with HSQC spectra will yield an NMR structure. We also find the overlaps among SG targets: 61% of SG protein sequences share at least 30% sequence identity with one or more other SG targets. There is no significant difference in average structure quality among SG structures and other structures in the PDB determined by "traditional" methods, but on average SG structures are deposited to the PDB twice as quickly after X-ray data collection.
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: O'Toole
authors.forename: Marek
authors.initials: M
authors.lastname: Grabowski
authors.forename: Zbyszek
authors.initials: Z
authors.lastname: Otwinowski
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Cygler
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003460:Crystallization; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D015870:Gene Expression; D023281:Genomics; D006801:Humans; D020407:Internet; D009316:National Institutes of Health (U.S.); D019906:Nuclear Magnetic Resonance, Biomolecular; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D014481:United States
chemical_list: D011506:Proteins