Threading with explicit models for evolutionary conservation of structure and sequence.
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.
Panchenko
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Computational Biology Branch, National Library of Medicine, National Institutes of Health Bethesda, Maryland 20894, USA.
Marchler-Bauer
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Bryant
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SH
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*
D011506:Proteins; D019757:Carbon-Oxygen Lyases; C021578:methylglyoxal synthase; D002222:Carbamoyl-Phosphate Synthase (Ammonia)