Two-state folding over a weak free-energy barrier.
We present a Monte Carlo study of a model protein with 54 amino acids that folds directly to its native three-helix-bundle state without forming any well-defined intermediate state. The free-energy barrier separating the native and unfolded states of this protein is found to be weak, even at the folding temperature. Nevertheless, we find that melting curves to a good approximation can be described in terms of a simple two-state system, and that the relaxation behavior is close to single exponential. The motion along individual reaction coordinates is roughly diffusive on timescales beyond the reconfiguration time for a single helix. A simple estimate based on diffusion in a square-well potential predicts the relaxation time within a factor of two.
Favrin
Giorgio
G
Complex Systems Division, Department of Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
Irbäck
Anders
A
Samuelsson
Björn
B
Wallin
Stefan
S
D000596:Amino Acids / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D007700:Kinetics; D015233:Models, Statistical; D009010:Monte Carlo Method; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors
D000596:Amino Acids; D011506:Proteins