Automated prediction of domain boundaries in CASP6 targets using Ginzu and RosettaDOM

TitleAutomated prediction of domain boundaries in CASP6 targets using Ginzu and RosettaDOM
Publication TypeJournal Article
Year of Publication2005
AuthorsKim, D. E., Chivian D., Malmström L., & Baker D.
Volume61 Suppl 7
Date Published2005
KeywordsAlgorithms, Amino Acid Sequence, Automation, Cluster Analysis, Computational Biology, Computer Simulation, Computers, Databases, Protein, Models, Molecular, Molecular Sequence Data, Primary Publication, Protein Conformation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Proteomics, Reproducibility of Results, Sequence Alignment, Software

Domain boundary prediction is an important step in both experimental and computational protein structure characterization. We have developed two fully automated domain parsing methods: the first, Ginzu, which we have described previously, utilizes information from homologous sequences and structures, while the second, RosettaDOM, which has not been described previously, uses only information in the query sequence. Ginzu iteratively assigns domains by homology to structures and sequence families using successively less confident methods. RosettaDOM uses the Rosetta de novo structure prediction method to build three-dimensional models, and then applies Taylor's structure based domain assignment method to parse the models into domains. Domain boundaries observed repeatedly in the models are predicted to be domain boundaries for the protein. Interestingly, RosettaDOM produced quite good domain predictions for proteins of a size typically considered to be beyond the reach of de novo structure prediction methods. For remote fold recognition targets and new folds, both Ginzu and RosettaDOM produced promising results, and in some cases where one method failed to detect the correct domain boundary, it was correctly identified by the other method. We describe here the successes and failures using both methods, and address the possibility of incorporating both protocols into an improved hybrid method.

Alternate JournalProteins
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