Excluded volume, local structural cooperativity,and the polymer physics of protein folding rates
arXiv:0706.0185 · doi:10.1073/pnas.0609321104
Abstract
A coarse-grained variational model is used to investigate the polymer dynamics of barrier crossing for a diverse set of two-state folding proteins. The model gives reliable folding rate predictions provided excluded volume terms that induce minor structural cooperativity are included in the interaction potential. In general, the cooperative folding routes have sharper interfaces between folded and unfolded regions of the folding nucleus and higher free energy barriers. The calculated free energy barriers are strongly correlated with native topology as characterized by contact order. Increasing the rigidity of the folding nucleus changes the local structure of the transition state ensemble non-uniformly across the set of protein studied. Neverthless, the calculated prefactors k0 are found to be relatively uniform across the protein set, with variation in 1/k0 less than a factor of five. This direct calculation justifies the common assumption that the prefactor is roughly the same for all small two-state folding proteins. Using the barrier heights obtained from the model and the best fit monomer relaxation time 30ns, we find that 1/k0 (1-5)us (with average 1/k0 4us). This model can be extended to study subtle aspects of folding such as the variation of the folding rate with stability or solvent viscosity, and the onset of downhill folding.
12 pages,6 figures,1 page supporting information.To be published in Proc.Natl.Acad.Sci.(USA)(2007)
References in corpus (7)
- Microscopic Theory of Protein Folding Rates.II: Local Reaction Coordinates and Chain Dynamics
- Variational theory for site resolved protein folding free energy surfaces
- Microscopic Theory of Protein Folding Rates.I: Fine Structure of the Free Energy Profile and Folding Routes from a Variational Approach
- Three-body Interactions Improve the Prediction of Rate and Mechanism in Protein Folding Models
- Non-Gaussian dynamics from a simulation of a short peptide: Loop closure rates and effective diffusion coefficients
- Effect of finite size on cooperativity and rates of protein folding
- Determination of barrier heights and prefactors from protein folding rate data