An analysis of protein folding pathways.
We have developed a model of the protein folding process based on three primary assumptions: that burying of hydrophobic area is the dominant contribution to the relative free energy of a conformation, that a record of the folding process is largely preserved in the final structure, and that the denatured state is a random coil. Detailed folding pathways are identified for 19 protein structures. The picture of the folding process that emerges from this analysis is one of nucleation by regions of 8-16 residues. Nucleation sites then lead to larger structures by two mechanisms: propagation and diffusion/collision. A Monte Carlo simulation is used to follow the folding pathway when propagation is the dominant mechanism. Because detailed pathways are derived for each protein, the models are susceptible to experimental verification.
Moult
J
J
Center for Advanced Research in Biotechnology, University of Maryland, Rockville 20850.
Unger
R
R
D000595:Amino Acid Sequence; D004798:Enzymes / Q000737:chemistry / Q000235:genetics; D008433:Mathematics; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
D004798:Enzymes; D011506:Proteins