Protein folding dynamics: quantitative comparison between theory and experiment.
The development of a quantitative kinetic scheme is a central goal in mechanistic studies of biological phenomena. For fast-folding proteins, which lack experimentally observable kinetic intermediates, a quantitative kinetic scheme describing the order and rate of events during folding has yet to be developed. In the present study, the folding mechanism of monomeric lambda repressor is described using the diffusion-collision model and estimates of intrinsic alpha-helix propensities. The model accurately predicts the folding rates of the wild-type protein and five of eight previously studied Ala left and right arrow Gly variants and suggests that the folding mechanism is distributed among multiple pathways that are highly sensitive to the amino acid sequence. For example, the model predicts that the wild-type protein folds through a small number of pathways with a folding time of 260 micros. However, the folding of a variant (G46A/G48A) is predicted to fold through a large number of pathways with a folding time of 12 micros. Both folding times quantitatively agree with the experimental values at 37 degrees C extrapolated to 0 M denaturant. The quantitative nature of the diffusion-collision model allows for rigorous experimental tests of the theory.
Burton
R E
RE
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Myers
J K
JK
Oas
T G
TG
D010582:Bacteriophage lambda; D004268:DNA-Binding Proteins; D004058:Diffusion; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry*; D012997:Solvents; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D012997:Solvents; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins