Automatic target selection for structural genomics on eukaryotes

Jinfeng Liu, Hedi Hegyi, Thomas B. Acton, Gaetano T. Montelione, Burkhard Rost

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

A central goal of structural genomics is to experimentally determine representative structures for all protein families. At least 14 structural genomics pilot projects are currently investigating the feasibility of high-throughput structure determination; the National Institutes of Health funded nine of these in the United States. Initiatives differ in the particular subset of "all families" on which they focus. At the NorthEast Structural Genomics consortium (NESG), we target eukaryotic protein domain families. The automatic target selection procedure has three aims: 1) identify all protein domain families from currently five entirely sequenced eukaryotic target organisms based on their sequence homology, 2) discard those families that can be modeled on the basis of structural information already present in the PDB, and 3) target representatives of the remaining families for structure determination. To guarantee that all members of one family share a common foldlike region, we had to begin by dissecting proteins into structural domain-like regions before clustering. Our hierarchical approach, CHOP, utilizing homology to PrISM, Pfam-A, and SWISS-PROT chopped the 103,796 eukaryotic proteins/ORFs into 247,222 fragments. Of these fragments, 122,999 appeared suitable targets that were grouped into >27,000 singletons and >18,000 multifragment clusters. Thus, our results suggested that it might be necessary to determine >40,000 structures to minimally cover the subset of five eukaryotic proteomes.

Original languageEnglish
Pages (from-to)188-200
Number of pages13
JournalProteins: Structure, Function and Genetics
Volume56
Issue number2
DOIs
Publication statusPublished - Aug 1 2004

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Keywords

  • Cluster
  • Domains
  • Protein structure family
  • Proteome analysis
  • Structural genomics
  • Target selection

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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