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Kinetic coupling between protein folding and prolyl isomerization. I. Theoretical models
T Kiefhaber1, H H Kohler, F X Schmid
1Laboratorium für Biochemie, Universität Bayreuth, Germany.
Journal of Molecular Biology
|March 5, 1992
Summary
Prolyl isomerization significantly impacts protein folding kinetics, especially when folding rates slow down. Understanding this coupling is crucial for accurate interpretation of folding data.
Area of Science:
- Protein dynamics
- Biophysical chemistry
- Computational biology
Background:
- Prolyl peptide bonds can isomerize, affecting protein folding.
- This isomerization can be a rate-limiting step in protein folding.
- Previous models often simplified or ignored this isomerization's kinetic impact.
Purpose of the Study:
- To model the influence of prolyl peptide bond isomerization on protein folding kinetics.
- To investigate how the number of prolyl residues affects folding rates.
- To determine conditions under which observed folding kinetics deviate from intrinsic rates.
Main Methods:
- Development of kinetic models for reversible protein folding.
- Simulations varying the number of prolyl residues and folding/isomerization rates.
- Analysis of observed rate constants under different kinetic regimes.
Main Results:
- Observed rate constants match intrinsic rates only when folding is much faster than prolyl isomerization.
- When folding and isomerization rates are comparable, observed kinetics become complex.
- Folding rates decrease with more prolyl residues, and apparent rates can be misinterpreted.
Conclusions:
- Prolyl isomerization significantly complicates protein folding kinetics.
- The coupling between folding and isomerization affects denaturant dependence.
- Tests are proposed to distinguish folding from isomerization contributions to observed kinetics.