Open AccessFast protein folding kinetics
Author(s) -
Jack Schonbrun,
Ken A. Dill
Publication year - 2003
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1735417100
Subject(s) - kinetics , folding (dsp implementation) , protein folding , downhill folding , exponential function , transition state theory , limiting , reaction coordinate , statistical physics , chemistry , simple (philosophy) , chemical physics , phi value analysis , thermodynamics , physics , computational chemistry , reaction rate constant , mathematics , classical mechanics , mechanical engineering , mathematical analysis , biochemistry , philosophy , epistemology , electrical engineering , engineering
Proteins are complex molecules, yet their folding kinetics is often fast (microseconds) and simple, involving only a single exponential function of time (called two-state kinetics). The main model for two-state kinetics has been transition-state theory, where an energy barrier defines a slow step to reach an improbable structure. But how can barriers explain fast processes, such as folding? We study a simple model with rigorous kinetics that explains the high speed instead as a result of the microscopic parallelization of folding trajectories. The single exponential results from a separation of timescales; the parallelization of routes is high at the start of folding and low thereafter. The ensemble of rate-limiting chain conformations is different from in transition-state theory; it is broad, overlaps with the denatured state, is not aligned along a single reaction coordinate, and involves well populated, rather than improbable, structures.