New Fold Methods: Prediction Reports

Rosetta predictions in CASP5: Successes, failures, and prospects for complete automation

  1. Philip Bradley,
  2. Dylan Chivian,
  3. Jens Meiler,
  4. Kira M.S. Misura,
  5. Carol A. Rohl†,¶,
  6. William R. Schief,
  7. William J. Wedemeyer‡,¶,
  8. Ora Schueler-Furman,
  9. Paul Murphy,
  10. Jack Schonbrun,
  11. Charles E.M. Strauss§,
  12. David Baker*

Article first published online: 15 OCT 2003

DOI: 10.1002/prot.10552

Issue

Proteins: Structure, Function, and Bioinformatics

Proteins: Structure, Function, and Bioinformatics

Supplement: Fifth Meeting on the Critical Assessment of Techniques for Protein Structure Prediction

Volume 53, Issue Supplement 6, pages 457–468, 2003

Additional Information

How to Cite

Bradley, P., Chivian, D., Meiler, J., Misura, K. M., Rohl, C. A., Schief, W. R., Wedemeyer, W. J., Schueler-Furman, O., Murphy, P., Schonbrun, J., Strauss, C. E. and Baker, D. (2003), Rosetta predictions in CASP5: Successes, failures, and prospects for complete automation. Proteins: Structure, Function, and Bioinformatics, 53: 457–468. doi: 10.1002/prot.10552

Author Information

  1. Department of Biochemistry, University of Washington, Seattle, Washington

  1. †

    Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064

  2. ‡

    Departments of Biochemistry and Physics, Michigan State University, East Lansing, MI 48824

  3. §

    Biosciences Division, Los Alamos National Laboratory, Los Alamos NM 87544

  1. P. Bradley, D. Chivian, J. Meiler, K.M.S. Misura, C.A. Rohl, W.R. Schief, and W.J. Wedemeyer contributed equally to this work.

*Department of Biochemistry, University of Washington, Box 357350, J-567 Health Sciences, Seattle, WA 98195-7350

Publication History

  1. Issue published online: 15 OCT 2003
  2. Article first published online: 15 OCT 2003
  3. Manuscript Accepted: 23 JUN 2003
  4. Manuscript Received: 1 MAR 2003

Funded by

  • Howard Hughes Medical Institute
  • Helen Hay Whitney Foundation
  • Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation
  • Human Frontier Science Program
  • National Institutes of Health. Grant Numbers: NRSA AR08558, T32 HG 00035

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Keywords:

  • protein structure prediction;
  • fragment insertion;
  • ROSETTA;
  • CASP;
  • full-atom refinement

Abstract

We describe predictions of the structures of CASP5 targets using Rosetta. The Rosetta fragment insertion protocol was used to generate models for entire target domains without detectable sequence similarity to a protein of known structure and to build long loop insertions (and N-and C-terminal extensions) in cases where a structural template was available. Encouraging results were obtained both for the de novo predictions and for the long loop insertions; we describe here the successes as well as the failures in the context of current efforts to improve the Rosetta method. In particular, de novo predictions failed for large proteins that were incorrectly parsed into domains and for topologically complex (high contact order) proteins with swapping of segments between domains. However, for the remaining targets, at least one of the five submitted models had a long fragment with significant similarity to the native structure. A fully automated version of the CASP5 protocol produced results that were comparable to the human-assisted predictions for most of the targets, suggesting that automated genomic-scale, de novo protein structure prediction may soon be worthwhile. For the three targets where the human-assisted predictions were significantly closer to the native structure, we identify the steps that remain to be automated. Proteins 2003;53:457–468. © 2003 Wiley-Liss, Inc.

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