Unraveling the structural characteristics of wild-type and mutant D178N of soluble dimeric prion protein at different pH values and temperatures: A molecular dynamics study

• Main Authors: Yung-YangChang, 張永源
• Other Authors: Chi-Chuan Hwang
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/56951004451010529433

碩士 === 國立成功大學 === 工程科學系碩博士班 === 100 === Prion disease is neurodegenerative diseases, also called transmissible spongiform encephalopathies (TSE). Such neurodegeneration event produces the structural misfolding from nomal PrPC to the pathogenic PrPSc. At present the PrPC how to transform into PrPSc pathway is still an open question. Furthermore, a growing body of evidence indicates that small, soluble oligomeric species generated from a variety of proteins and peptides rather than mature amyloid fibrils are inherently highly cytotoxicity. Due to the structure of dimeric prion is belongs to the simplest aggregates form that eventually elongate to the oligomeric. In this study, the wild-type and mutant D178N of soluble dimeric prion protein at different pH values and temperatures are examined using molecular dynamics simulations. In order to treat the structure-toxicity relationship, some parameters are analyzed, e.g. RMSD, RMSF, Rg, DSSP, salt bridge, hydrogen bond numbers and so on. On the other hand, three dimensional domain-swapping-dependent oligomerization is considered an important step in the conformational change of PrPC to PrPSc, but the function and dynamics of the dimeric form of PrP is unknown. Therefore we also examined and compared the domain swapping and non-swapping phenomenon of wild-type and mutant D178N of prion dimers at different circumstance. The significant result shown that domain swapping is contrived only in wild-type dimer, nevertheless, mutant D178N of prion dimer is not contrived domain swapping. Such diverse aggregates behaviors may help us to deeply understand the further aggregation process.