title: Tuning the Attempt Frequency of Protein Folding Dynamics via  Transition-State Rigidification: Application to Trp-Cage.
abstract: The attempt frequency or prefactor (k0) of the transition-state rate equation of protein folding kinetics has been estimated to be on the order of 10(6) s(-1), which is many orders of magnitude smaller than that of chemical reactions. Herein we use the mini-protein Trp-cage to show that it is possible to significantly increase the value of k0 for a protein folding reaction by rigidifying the transition state. This is achieved by reducing the conformational flexibility of a key structural element (i.e., an α-helix) formed in the transition state via photoisomerization of an azobenzene cross-linker. We find that this strategy not only decreases the folding time of the Trp-cage peptide by more than an order of magnitude (to ∼100 ns at 25°C) but also exposes parallel folding pathways, allowing us to provide, to the best of our knowledge, the first quantitative assessment of the curvature of the transition-state free-energy surface of a protein.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Abaskharon
authors.forename: Robert M
authors.initials: RM
authors.lastname: Culik
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Woolley
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
mesh_terms: D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D010455:Peptides; C508725:Trp-cage peptide