Addressing the intrinsic disorder bottleneck in structural proteomics

Christopher J. Oldfield, Eldon L. Ulrich, Yugong Cheng, A. Keith Dunker, John L. Markley

Research output: Contribution to journalArticle

70 Scopus citations


The Center for Eukaryotic Structural Genomics (CESG), as part of the Protein Structure Initiative (PSI), has established a high-throughput structure determination pipeline focused on eukaryotic proteins. NMR spectroscopy is an integral part of this pipeline, both as a method for structure determinations and as a means for screening proteins for stable structure. Because computational approaches have estimated that many eukaryotic proteins are highly disordered, about 1 year into the project, CESG began to use an algorithm (the Predictor of Naturally Disordered Regions, PONDR®) to avoid proteins that were likely to be disordered. We report a retrospective analysis of the effect of this filtering on the yield of viable structure determination candidates. In addition, we have used our current database of results on 70 protein targets from Arabidopsis thaliana and 1 from Caenorhabditis elegans, which were labeled uniformly with nitrogen-15 and screened for disorder by NMR spectroscopy, to compare the original algorithm with 13 other approaches for predicting disorder from sequence. Our study indicates that the efficiency of structural proteomics of eukaryotes can be improved significantly by removing targets predicted to be disordered by an algorithm chosen to provide optimal performance.

Original languageEnglish (US)
Pages (from-to)444-453
Number of pages10
JournalProteins: Structure, Function and Genetics
Issue number3
StatePublished - May 15 2005


  • Dynamic disorder
  • NMR spectroscopy
  • Protein Structure Initiative
  • Receiver operating characteristic curve
  • Structural genomics

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

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