TY - JOUR
T1 - Exploring structural and thermodynamic stabilities of human prion protein pathogenic mutants D202N, E211Q and Q217R
AU - Guo, Jingjing
AU - Ren, Hui
AU - Ning, Lulu
AU - Liu, Huanxiang
AU - Yao, Xiaojun
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grants No.: 20905033 and 21103075 ). We would like to thank the Gansu Computing Center for providing the computing resources.
PY - 2012/6
Y1 - 2012/6
N2 - The central event in the pathogenesis of prion protein (PrP) is a profound conformational change from its α-helical (PrPC) to its β-sheet-rich isoform (PrPSc). Many single amino acid mutations of PrP are associated with familial prion diseases, such as D202N, E211Q, and Q217R mutations located at the third native α-helix of human PrP. In order to explore the underlying structural and dynamic effects of these mutations, we performed all-atom molecular dynamics (MD) simulations for the wild-type (WT) PrP and its mutants. The obtained results indicate that these amino acid substitutions have subtle effects on the protein structures, but show large changes of the overall electrostatic potential distributions. We can infer that the changes of PrP electrostatic surface due to the studied mutations may influence the intermolecular interactions during the aggregation process. In addition, the mutations also affect the thermodynamic stabilities of PrP.
AB - The central event in the pathogenesis of prion protein (PrP) is a profound conformational change from its α-helical (PrPC) to its β-sheet-rich isoform (PrPSc). Many single amino acid mutations of PrP are associated with familial prion diseases, such as D202N, E211Q, and Q217R mutations located at the third native α-helix of human PrP. In order to explore the underlying structural and dynamic effects of these mutations, we performed all-atom molecular dynamics (MD) simulations for the wild-type (WT) PrP and its mutants. The obtained results indicate that these amino acid substitutions have subtle effects on the protein structures, but show large changes of the overall electrostatic potential distributions. We can infer that the changes of PrP electrostatic surface due to the studied mutations may influence the intermolecular interactions during the aggregation process. In addition, the mutations also affect the thermodynamic stabilities of PrP.
KW - D202N/E211Q/Q217R mutants
KW - Familial prion diseases
KW - MM-GBSA method
KW - Molecular dynamics simulation
KW - Prion protein (PrP)
UR - http://www.scopus.com/inward/record.url?scp=84861481443&partnerID=8YFLogxK
U2 - 10.1016/j.jsb.2012.03.009
DO - 10.1016/j.jsb.2012.03.009
M3 - Article
C2 - 22491059
AN - SCOPUS:84861481443
SN - 1047-8477
VL - 178
SP - 225
EP - 232
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 3
ER -
