English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Enhancing NMR derived ensembles with kinetics on multiple timescales.

MPS-Authors
/persons/resource/persons82288

Smith,  C. A.
Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons37446

Mazur,  A.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons228271

Rout,  A. K.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons14824

Becker,  S.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15424

Lee,  D.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons14970

de Groot,  B. L.
Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15147

Griesinger,  C.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)

3182493.pdf
(Publisher version), 2MB

Supplementary Material (public)

3182493_Suppl.pdf
(Supplementary material), 763KB

Citation

Smith, C. A., Mazur, A., Rout, A. K., Becker, S., Lee, D., de Groot, B. L., et al. (2020). Enhancing NMR derived ensembles with kinetics on multiple timescales. Journal of Biomolecular NMR, 74(1), 27-43. doi:10.1007/s10858-019-00288-8.


Cite as: http://hdl.handle.net/21.11116/0000-0005-5D70-5
Abstract
Nuclear magnetic resonance (NMR) has the unique advantage of elucidating the structure and dynamics of biomolecules in solution at physiological temperatures, where they are in constant movement on timescales from picoseconds to milliseconds. Such motions have been shown to be critical for enzyme catalysis, allosteric regulation, and molecular recognition. With NMR being particularly sensitive to these timescales, detailed information about the kinetics can be acquired. However, nearly all methods of NMR-based biomolecular structure determination neglect kinetics, which introduces a large approximation to the underlying physics, limiting both structural resolution and the ability to accurately determine molecular flexibility. Here we present the Kinetic Ensemble approach that uses a hierarchy of interconversion rates between a set of ensemble members to rigorously calculate Nuclear Overhauser Effect (NOE) intensities. It can be used to simultaneously refine both temporal and structural coordinates. By generalizing ideas from the extended model free approach, the method can analyze the amplitudes and kinetics of motions anywhere along the backbone or side chains. Furthermore, analysis of a large set of crystal structures suggests that NOE data contains a surprising amount of high-resolution information that is better modeled using our approach. The Kinetic Ensemble approach provides the means to unify numerous types of experiments under a single quantitative framework and more fully characterize and exploit kinetically distinct protein states. While we apply the approach here to the protein ubiquitin and cross validate it with previously derived datasets, the approach can be applied to any protein for which NOE data is available.