Kinetic pathways of beta-hairpin (un)folding in explicit solvent.
We examine the dynamical (un)folding pathways of the C-terminal beta-hairpin of protein G-B1 at room temperature in explicit solvent, by employing transition path sampling algorithms. The path ensembles contain information on the folding kinetics, including solvent motion. We determine the transition state ensembles for the two main transitions: 1), the hydrophobic collapse; and 2), the backbone hydrogen bond formation. In both cases the transition state ensembles are characterized by a layer (1) or a strip (2) of water molecules in between the two hairpin strands, supporting the hypothesis of the solvent as lubricant in the folding process. The transition state ensembles do not correspond with saddle points in the equilibrium free-energy landscapes. The kinetic pathways are thus not completely determined by the free-energy landscape. This phenomenon can occur if the order parameters obey different timescales. Using the transition interface sampling technique, we calculate the rate constants for (un)folding and find them in reasonable agreement with experiments, thus supporting the validation of using all-atom force fields to study protein folding.
Bolhuis
Peter G
PG
The van 't Hoff Institute for Molecular Sciences, Chemistry Department, University of Amsterdam, Amsterdam, The Netherlands. bolhuis@science.uva.nl
D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D019295:Computational Biology / Q000379:methods; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents; D013305:Streptomyces griseus / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D012997:Solvents