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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
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    Citations

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    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. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    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.

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