By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (mu s 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 Munoz et al. [Munoz 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 (similar to 5 mu s) in excellent agreement with the experimentally observed one (similar to 6 mu s). 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, I., D'Abramo, M., Di Nola, A., Amadei, A. (2005). Theoretical characterization of alpha-helix and beta-hairpin folding kinetics. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 127(42), 14825-14832 [10.1021/ja053383f].
Theoretical characterization of alpha-helix and beta-hairpin folding kinetics
AMADEI, ANDREA
2005-01-01
Abstract
By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (mu s 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 Munoz et al. [Munoz 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 (similar to 5 mu s) in excellent agreement with the experimentally observed one (similar to 6 mu s). 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.