Theoretical characterization of alpha-helix and beta-hairpin folding kinetics.
By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (mus time scale), we model the folding kinetics of alpha-helix and beta-hairpin peptides as a diffusive process over the free energy surface. The two model systems studied in this paper (the alpha-helical temporin L and the beta-hairpin prion protein H1 peptide) exhibit a funnel-like almost barrierless free energy profile, leading to nonexponential folding kinetics matching rather well the available experimental data. Moreover, using the free energy profile provided by Muñoz et al. [Muñoz et al. Nature 1997, 390: 196-199], this model was also applied to reproduce the two-state folding kinetics of the C-terminal beta-hairpin of protein GB1, yielding an exponential folding kinetics with a time constant (approximately 5 micros) in excellent agreement with the experimentally observed one (approximately 6 micros). Finally, the folding kinetics obtained by solving the diffusion equation, considering either a one-dimensional or a two-dimensional free energy surface, are also compared in order to understand the relevance of the possible kinetic coupling between conformational degrees of freedom in the folding process.
Daidone
Isabella
I
Department of Chemistry, University of Rome La Sapienza, P.le Aldo Moro 5, 00185 Rome, Italy.
D'Abramo
Marco
M
Di Nola
Alfredo
A
Amadei
Andrea
A
D004058:Diffusion; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013499:Surface Properties; D013997:Time Factors
D010455:Peptides