title: Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins.
abstract: Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small, fast-folding proteins. To investigate the extent of the topological control of the folding process, we studied the folding of simplified models of five small globular proteins constructed using a Go-like potential to retain the information about the native structures but drastically reduce the energetic frustration and energetic heterogeneity among residue-residue native interactions. By comparing the structure of the transition state ensemble (experimentally determined by Phi-values) and of the intermediates with those obtained using our models, we show that these energetically unfrustrated models can reproduce the global experimentally known features of the transition state ensembles and "en-route" intermediates, at least for the analyzed proteins. This result clearly indicates that, as long as the protein sequence is sufficiently minimally frustrated, topology plays a central role in determining the folding mechanism.
authors.affiliation: Department of Physics, University of California at San Diego, La Jolla, CA 92093-0319, USA. cclementi@ucsd.edu
authors.forename: C
authors.initials: C
authors.lastname: Clementi
authors.forename: H
authors.initials: H
authors.lastname: Nymeyer
authors.forename: J N
authors.initials: JN
authors.lastname: Onuchic
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010940:Plant Proteins; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016914:Ribonuclease H / Q000737:chemistry / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D010455:Peptides; D010940:Plant Proteins; D011506:Proteins; C093336:chymotrypsin inhibitor 2; D012260:Ribonucleases; D016914:Ribonuclease H; C019760:Bacillus amyloliquefaciens ribonuclease