Release Time:2019-03-09  Hits:

Indexed by: Journal Article

Date of Publication: 2013-12-01

Journal: JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY

Included Journals: Scopus、SCIE

Volume: 12

Issue: 8

ISSN: 0219-6336

Key Words: Prion protein; fold; Go model; cooperativity; stability

Abstract: Prions are associated with neurodegenerative diseases induced by transmissible spongiform encephalopathies. The infectious scrapie form is referred to as PrPSc, which has conformational change from normal prion with predominant alpha-helical conformation to the abnormal PrPSc that is rich in beta-sheet content. Neurodegenerative diseases have been found from both human and bovine sources, but there are no reports about infected by transmissible spongiform encephalopathies from rabbit, canine and horse sources. Here we used coarse-grained G (o) over bar model to compare the difference among human, bovine, rabbit, canine, and horse normal (cellular) prion proteins. The denatured state of normal prion has relation with the conversion from normal to abnormal prion protein, so we used all-atom G (o) over bar model to investigate the folding pathway and energy landscape for human prion protein. Through using coarse-grained G (o) over bar model, the cooperativity of the five prion proteins was characterized in terms of calorimetric criterion, sigmoidal transition, and free-energy profile. The rabbit and horse prion proteins have higher folding free-energy barrier and cooperativity, and canine prion protein has slightly higher folding free-energy barrier comparing with human and bovine prion proteins. The results from all-atom Go model confirmed the validity of C-alpha-G (o) over bar model. The correlations of our results with previous experimental and theoretical researches were discussed.