Large scale determination of previously unsolved protein structures using evolutionary information

  1. Sergey Ovchinnikov
  2. Lisa Kinch
  3. Hahnbeom Park
  4. Yuxing Liao
  5. Jimin Pei
  6. David E Kim
  7. Hetunandan Kamisetty
  8. Nick V Grishin
  9. David Baker  Is a corresponding author
  1. University of Washington, United States
  2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States
  3. University of Texas Southwestern Medical Center, United States
  4. Facebook Inc., United States

Abstract

The prediction of the structures of proteins without detectablesequence similarity to any protein of known structure remains anoutstanding scientific challenge. Here we describe de novo blindstructure predictions of unprecedented accuracy for two proteins in large families made in the recent CASP11 blind test of protein structure prediction methods by incorporating residue-residue co-evolution information in the Rosetta structure prediction program. We then use the method to generate structure models for 58 of the 121 large protein families in prokaryotes for which three dimensionalstructures are not available. These models, which are posted online for public access, provide structural information for the over 400,000 proteins belonging to the 58 families and suggest hypotheses about mechanism for the subset for which the function is known, and hypotheses about function for the remainder.

Article and author information

Author details

  1. Sergey Ovchinnikov

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lisa Kinch

    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hahnbeom Park

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuxing Liao

    Department of Biophysics, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jimin Pei

    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. David E Kim

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hetunandan Kamisetty

    Facebook Inc., Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nick V Grishin

    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David Baker

    Department of Biochemistry, University of Washington, Seattle, United States
    For correspondence
    dabaker@uw.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Yibing Shan, DE Shaw Research, United States

Version history

  1. Received: June 6, 2015
  2. Accepted: August 30, 2015
  3. Accepted Manuscript published: September 3, 2015 (version 1)
  4. Version of Record published: October 21, 2015 (version 2)

Copyright

© 2015, Ovchinnikov et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sergey Ovchinnikov
  2. Lisa Kinch
  3. Hahnbeom Park
  4. Yuxing Liao
  5. Jimin Pei
  6. David E Kim
  7. Hetunandan Kamisetty
  8. Nick V Grishin
  9. David Baker
(2015)
Large scale determination of previously unsolved protein structures using evolutionary information
eLife 4:e09248.
https://doi.org/10.7554/eLife.09248

Share this article

https://doi.org/10.7554/eLife.09248

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