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Related Experiment Videos

Different circular permutations produced different folding nuclei in proteins: a computational study.

L Li1, E I Shakhnovich

  • 1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, 02138, USA.

Journal of Molecular Biology
|February 17, 2001
PubMed
Summary
This summary is machine-generated.

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Circular permutation impacts protein folding nucleus and kinetics. One circular permutant (CP2) retained the wild-type folding nucleus and kinetics, despite an intermediate state, while CP1 showed altered folding pathways.

Area of Science:

  • Protein Folding Dynamics
  • Biophysical Chemistry
  • Computational Biology

Background:

  • Circular permutation studies on protein folding pathways have yielded conflicting results.
  • Understanding how circular permutations affect protein transition states is crucial for protein engineering and drug design.

Purpose of the Study:

  • To investigate the impact of circular permutation on the folding nucleus and kinetics of a lattice protein model.
  • To clarify the role of the folding nucleus in protein folding pathways and the interpretation of experimental data.

Main Methods:

  • Studied two circular permutations (CP1, CP2) of a lattice protein model with side-chains.
  • Analyzed native states, folding nuclei, folding kinetics, and intermediate states of wild-type and permuted sequences.

Related Experiment Videos

  • Compared folding behaviors to interpret the influence of permutation sites on folding pathways.

    • Main Results:

    • Both circular permutations (CP1, CP2) maintained the native state of the wild-type sequence.
    • CP1, permuted at the wild-type folding nucleus, exhibited a different nucleus and slower folding.
    • CP2, permuted at an unstructured site, retained the wild-type nucleus and folding rate, but showed multi-state folding with a native-like intermediate. This intermediate's stabilization by mixed interactions challenges simple on/off-pathway classifications.

    Conclusions:

    • Circular permutation's effect on protein folding is site-specific, influencing the folding nucleus and kinetics.
    • The presence and nature of folding intermediates require careful interpretation, especially regarding their pathway classification.
    • This study supports using circular permutations to identify protein nucleation sites and clarifies previous experimental findings.