IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v433y2005i7022d10.1038_nature03199.html
   My bibliography  Save this article

Simultaneous determination of protein structure and dynamics

Author

Listed:
  • Kresten Lindorff-Larsen

    (University of Cambridge
    Institute of Molecular Biology, University of Copenhagen)

  • Robert B. Best

    (University of Cambridge
    National Institutes of Health)

  • Mark A. DePristo

    (University of Cambridge
    Harvard University)

  • Christopher M. Dobson

    (University of Cambridge)

  • Michele Vendruscolo

    (University of Cambridge)

Abstract

We present a protocol for the experimental determination of ensembles of protein conformations that represent simultaneously the native structure and its associated dynamics. The procedure combines the strengths of nuclear magnetic resonance spectroscopy—for obtaining experimental information at the atomic level about the structural and dynamical features of proteins—with the ability of molecular dynamics simulations to explore a wide range of protein conformations. We illustrate the method for human ubiquitin in solution and find that there is considerable conformational heterogeneity throughout the protein structure. The interior atoms of the protein are tightly packed in each individual conformation that contributes to the ensemble but their overall behaviour can be described as having a significant degree of liquid-like character. The protocol is completely general and should lead to significant advances in our ability to understand and utilize the structures of native proteins.

Suggested Citation

  • Kresten Lindorff-Larsen & Robert B. Best & Mark A. DePristo & Christopher M. Dobson & Michele Vendruscolo, 2005. "Simultaneous determination of protein structure and dynamics," Nature, Nature, vol. 433(7022), pages 128-132, January.
    • Handle: RePEc:nat:nature:v:433:y:2005:i:7022:d:10.1038_nature03199
    DOI: 10.1038/nature03199
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature03199
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature03199?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Anders S Christensen & Troels E Linnet & Mikael Borg & Wouter Boomsma & Kresten Lindorff-Larsen & Thomas Hamelryck & Jan H Jensen, 2013. "Protein Structure Validation and Refinement Using Amide Proton Chemical Shifts Derived from Quantum Mechanics," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-10, December.
    2. F. Emil Thomasen & Tórur Skaalum & Ashutosh Kumar & Sriraksha Srinivasan & Stefano Vanni & Kresten Lindorff-Larsen, 2024. "Rescaling protein-protein interactions improves Martini 3 for flexible proteins in solution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Timothy R Lezon & Ivet Bahar, 2010. "Using Entropy Maximization to Understand the Determinants of Structural Dynamics beyond Native Contact Topology," PLOS Computational Biology, Public Library of Science, vol. 6(6), pages 1-12, June.
    4. Dong Long & Rafael Brüschweiler, 2011. "In Silico Elucidation of the Recognition Dynamics of Ubiquitin," PLOS Computational Biology, Public Library of Science, vol. 7(4), pages 1-9, April.
    5. Douglas L Theobald & Deborah S Wuttke, 2008. "Accurate Structural Correlations from Maximum Likelihood Superpositions," PLOS Computational Biology, Public Library of Science, vol. 4(2), pages 1-8, February.
    6. Wouter Boomsma & Jesper Ferkinghoff-Borg & Kresten Lindorff-Larsen, 2014. "Combining Experiments and Simulations Using the Maximum Entropy Principle," PLOS Computational Biology, Public Library of Science, vol. 10(2), pages 1-9, February.
    7. Nimmi Das Anthuparambil & Anita Girelli & Sonja Timmermann & Marvin Kowalski & Mohammad Sayed Akhundzadeh & Sebastian Retzbach & Maximilian D. Senft & Michelle Dargasz & Dennis Gutmüller & Anusha Hire, 2023. "Exploring non-equilibrium processes and spatio-temporal scaling laws in heated egg yolk using coherent X-rays," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Kresten Lindorff-Larsen & Jesper Ferkinghoff-Borg, 2009. "Similarity Measures for Protein Ensembles," PLOS ONE, Public Library of Science, vol. 4(1), pages 1-13, January.
    9. Gregory D Friedland & Nils-Alexander Lakomek & Christian Griesinger & Jens Meiler & Tanja Kortemme, 2009. "A Correspondence Between Solution-State Dynamics of an Individual Protein and the Sequence and Conformational Diversity of its Family," PLOS Computational Biology, Public Library of Science, vol. 5(5), pages 1-16, May.
    10. Kai Wang & Shiyang Long & Pu Tian, 2015. "Hierarchical Conformational Analysis of Native Lysozyme Based on Sub-Millisecond Molecular Dynamics Simulations," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-17, June.
    11. Matteo Tiberti & Elena Papaleo & Tone Bengtsen & Wouter Boomsma & Kresten Lindorff-Larsen, 2015. "ENCORE: Software for Quantitative Ensemble Comparison," PLOS Computational Biology, Public Library of Science, vol. 11(10), pages 1-16, October.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:433:y:2005:i:7022:d:10.1038_nature03199. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.