title: General mechanism of two-state protein folding kinetics.
abstract: We describe here a general model of the kinetic mechanism of protein folding. In the Foldon Funnel Model, proteins fold in units of secondary structures, which form sequentially along the folding pathway, stabilized by tertiary interactions. The model predicts that the free energy landscape has a volcano shape, rather than a simple funnel, that folding is two-state (single-exponential) when secondary structures are intrinsically unstable, and that each structure along the folding path is a transition state for the previous structure. It shows how sequential pathways are consistent with multiple stochastic routes on funnel landscapes, and it gives good agreement with the 9 order of magnitude dependence of folding rates on protein size for a set of 93 proteins, at the same time it is consistent with the near independence of folding equilibrium constant on size. This model gives estimates of folding rates of proteomes, leading to a median folding time in Escherichia coli of about 5 s.
authors: Department of Biochemistry and Biophysics, University of California , San Francisco, California 94143, United States.
authors: Geoffrey C
authors: GC
authors: Rollins
authors: Ken A
authors: KA
authors: Dill
mesh_terms: D016880:Anisotropy; D001704:Biopolymers / Q000737:chemistry*; D002164:Camphor / Q000737:chemistry*; D017666:Deuterium Oxide / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D009930:Organic Chemicals; D010087:Oxides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry
chemical_list: D001704:Biopolymers; D009930:Organic Chemicals; D010087:Oxides; D011506:Proteins; D012996:Solutions; D012997:Solvents; D013395:Sucrose; D002164:Camphor; D006108:Graphite; D011392:Proline; D017666:Deuterium Oxide