Fold recognition from sequence comparisons

Proteins. 2001;Suppl 5:68-75. doi: 10.1002/prot.10000.

Abstract

We applied a new protocol based on PSI-Blast to predict the structures of fold recognition targets during CASP4. The protocol used a back-validation step to infer biologically significant connections between sequences with PSI-Blast E-values up to 10. If connections were found to proteins of known structure, alignments were generated by using HMMer. The protocol was implemented in a fully automated version (SBauto) and in a version that allowed manual intervention (SBfold). We found that the automated version made 17 predictions for target domains, of which 8 identified the correct fold with an average alignment accuracy of 24% for alignable residues and 43% for equivalent secondary structure elements. The manual version improved predictions somewhat, with 10 of 15 predictions identifying the correct fold with alignment accuracies of 33% for alignable residues and 64% for equivalent secondary structure elements. We describe successes and failures of our approach and discuss future developments of fold recognition.

MeSH terms

  • Acid Anhydride Hydrolases / chemistry
  • Amino Acid Sequence
  • Automation
  • Bacterial Proteins / chemistry
  • Carboxylic Ester Hydrolases / chemistry
  • Computer Simulation
  • Databases, Protein
  • Geobacillus stearothermophilus
  • Glycoside Hydrolases / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleoside-Triphosphatase
  • Polysaccharide-Lyases / chemistry
  • Protein Conformation*
  • Protein Folding*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment*
  • Sequence Analysis, Protein
  • Software
  • Streptococcus mutans
  • Transcription Factors / chemistry

Substances

  • Bacterial Proteins
  • Spo0A protein, Bacillus subtilis
  • Transcription Factors
  • Carboxylic Ester Hydrolases
  • pectinesterase
  • Glycoside Hydrolases
  • protopectinase
  • Acid Anhydride Hydrolases
  • Nucleoside-Triphosphatase
  • Polysaccharide-Lyases
  • pectate lyase