TY - JOUR
T1 - Comparison of the unfolding and oligomerization of human prion protein under acidic and neutral environments by molecular dynamics simulations
AU - Gao, Ya
AU - Zhu, Tong
AU - Zhang, Chaomin
AU - Zhang, John Z.H.
AU - Mei, Ye
N1 - Funding Information:
This work is supported by the National Natural Science Foundation of China (Grant Nos. 21503132 and 21773066 ), National Program on Key Project ( 2016YFA0501700 ), Innovation Program of Shanghai Municipal Education Commission ( 201701070005E00020 ), Shanghai Municipal Education Commission ( 15CG59 ), NYU Global Seed Grant , China Postdoctoral Science Foundation , the Talent Program of Shanghai University of Engineering Science , and the Large Instruments Open Foundation of East China Normal University . We thank Supercomputer Center of East China Normal University for CPU time support.
Publisher Copyright:
© 2018
PY - 2018/8/16
Y1 - 2018/8/16
N2 - Aggregation of the misfolded scrapie prion protein (PrPSc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrPC by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrPC starts from the opening of the folded domain with α1 moving away from α2α3 domain, and then arrives at a metastable intermediate, and forms a more stable dimer complex in the end. This work unravels the mechanism of the early stage of conformational conversion and dimerization of prion protein and provides significant hints for the development of anti-prion therapeutics.
AB - Aggregation of the misfolded scrapie prion protein (PrPSc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrPC by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrPC starts from the opening of the folded domain with α1 moving away from α2α3 domain, and then arrives at a metastable intermediate, and forms a more stable dimer complex in the end. This work unravels the mechanism of the early stage of conformational conversion and dimerization of prion protein and provides significant hints for the development of anti-prion therapeutics.
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U2 - 10.1016/j.cplett.2018.07.014
DO - 10.1016/j.cplett.2018.07.014
M3 - Article
AN - SCOPUS:85049756058
VL - 706
SP - 594
EP - 600
JO - Chemical Physics Letters
JF - Chemical Physics Letters
SN - 0009-2614
ER -