title: Threading with explicit models for evolutionary conservation of structure and sequence.
abstract: We have attempted to predict the three-dimensional structures of 19 proteins for the CASP3 experiment, each showing less than 25% sequence identity with known structures. Predictions were based on a threading method that aligns the target sequence with the conserved cores of structural templates, as identified from structure-structure alignments of the template with homologous neighbors. Alternative alignments were scored using contact potentials and a position-specific score matrix derived from sequence neighbors of the template. We find that this method identified the correct structural family for 11 of the 19 targets and predicted the remaining 8 targets to be similar to "none" of the templates, avoiding false positives. Threading alignments are relatively accurate for 10 of the 11 targets, including alignments for 6 of 7 identified at CASP3 as fold-recognition targets. These predictions were ranked "first place" by the CASP3 assessor when compared to fold-recognition predictions made by other methods. It appears that threading with family-specific models for structure and sequence conservation has improved threading prediction accuracy.
authors.affiliation: Computational Biology Branch, National Library of Medicine, National Institutes of Health Bethesda, Maryland 20894, USA.
authors.forename: A
authors.initials: A
authors.lastname: Panchenko
authors.forename: A
authors.initials: A
authors.lastname: Marchler-Bauer
authors.forename: S H
authors.initials: SH
authors.lastname: Bryant
mesh_terms: D000465:Algorithms; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000737:chemistry; D019757:Carbon-Oxygen Lyases / Q000737:chemistry; D017124:Conserved Sequence; D004926:Escherichia coli / Q000201:enzymology; D019143:Evolution, Molecular; D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D019757:Carbon-Oxygen Lyases; C021578:methylglyoxal synthase; D002222:Carbamoyl-Phosphate Synthase (Ammonia)