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.
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore CHIM/02 - CHIMICA FISICA
English
Data reduction; Degrees of freedom (mechanics); Diffusion; Free energy; Molecular dynamics; Proteins; Diffusion coefficients; Folding kinetics; Folding processes; Kinetic couplings; Kinetic energy; cell protein; protein GB1; unclassified drug; alpha helix; article; beta hairpin folding; binding kinetics; carboxy terminal sequence; conformation; diffusion; diffusion coefficient; energy; molecular dynamics; protein folding; simulation; surface property; theoretical model; Diffusion; Kinetics; Models, Chemical; Peptides; Protein Folding; Protein Structure, Secondary; Surface Properties; Time Factors
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].
Daidone, I; D'Abramo, M; Di Nola, A; Amadei, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34902
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