Theoretical Characterization of -Helix and -Hairpin Folding Kinetics

Isabella Daidone, Marco D'Abramo, Alfredo Di Nola, and Andrea Amadei*

Contribution from the Department of Chemistry, University of Rome "La Sapienza", P.le Aldo Moro 5, 00185 Rome, Italy, and Dipartimento di Scienze e Tecnologie Chimiche, University of Rome "Tor Vergata", via della Ricerca Scientifica 1, I-00133 Rome, Italy

Received May 24, 2005

FULL TEXT

Abstract:

By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (s time scale), we model the folding kinetics of -helix and -hairpin peptides as a diffusive process over the free energy surface. The two model systems studied in this paper (the -helical temporin L and the -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 -hairpin of protein GB1, yielding an exponential folding kinetics with a time constant (~5 s) in excellent agreement with the experimentally observed one (~6 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.