title: Fold recognition from sequence comparisons.
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.
authors.affiliation: Protein Bioinformatics Group, GlaxoSmithKline, Collegeville, Pennsylvania 19426-0989, USA. Kristin.K.Koretke@gsk.com
authors.forename: K K
authors.initials: KK
authors.lastname: Koretke
authors.forename: R B
authors.initials: RB
authors.lastname: Russell
authors.forename: A N
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry; D000595:Amino Acid Sequence; D001331:Automation; D001426:Bacterial Proteins / Q000737:chemistry; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry; D003198:Computer Simulation; D030562:Databases, Protein; D001411:Geobacillus stearothermophilus; D006026:Glycoside Hydrolases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D043583:Nucleoside-Triphosphatase; D011133:Polysaccharide-Lyases / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D012984:Software; D013295:Streptococcus mutans; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C080950:Spo0A protein, Bacillus subtilis; D014157:Transcription Factors; D002265:Carboxylic Ester Hydrolases; C022323:pectinesterase; D006026:Glycoside Hydrolases; C083413:protopectinase; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D011133:Polysaccharide-Lyases; C023911:pectate lyase