title: Folding behavior of ribosomal protein S6 studied by modified Gō-like model.
abstract: Recent experimental and theoretical studies suggest that, although topology is the determinant factor in protein folding, especially for small single-domain proteins, energetic factors also play an important role in the folding process. The ribosomal protein S6 has been subjected to intensive studies. A radical change of the transition state in its circular permutants has been observed, which is believed to be caused by a biased distribution of contact energies. Since the simplistic topology-only Gō-like model is not able to reproduce such an observation, we modify the model by introducing variable contact energies between residues based on their physicochemical properties. The modified Gō-like model can successfully reproduce the Phi-value distributions, folding nucleus, and folding pathways of both the wild-type and circular permutants of S6. Furthermore, by comparing the results of the modified and the simplistic models, we find that the hydrophobic effect constructs the major force that balances the loop entropies. This may indicate that nature maintains the folding cooperativity of this protein by carefully arranging the location of hydrophobic residues in the sequence. Our study reveals a strategy or mechanism used by nature to get out of the dilemma when the native structure, possibly required by biological function, conflicts with folding cooperativity. Finally, the possible relationship between such a design of nature and amyloidosis is also discussed.
authors.affiliation: National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, 210093 China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: W F
authors.initials: WF
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D038601:Ribosomal Protein S6 / Q000737:chemistry* / Q000648:ultrastructure*; D013329:Structure-Activity Relationship
chemical_list: D038601:Ribosomal Protein S6