Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.

Prion diseases are marked by cerebral accumulation of the abnormal isoform of the prion protein. A fragment of prion protein composed of residues 106-126 (PrP106-126) exhibits similar properties to full length prion and plays a key role in the conformational conversion from cellular prion to its pat...

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Autores principales:	Lulu Ning, Jingjing Guo, Qifeng Bai, Nengzhi Jin, Huanxiang Liu, Xiaojun Yao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/65dcfc70056f434baecb14715d468476
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spelling	oai:doaj.org-article:65dcfc70056f434baecb14715d4684762021-11-18T08:32:07ZStructural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.1932-620310.1371/journal.pone.0087266https://doaj.org/article/65dcfc70056f434baecb14715d4684762014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586266/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Prion diseases are marked by cerebral accumulation of the abnormal isoform of the prion protein. A fragment of prion protein composed of residues 106-126 (PrP106-126) exhibits similar properties to full length prion and plays a key role in the conformational conversion from cellular prion to its pathogenic pattern. Soluble oligomers of PrP106-126 have been proposed to be responsible for neurotoxicity. However, the monomeric conformational space and initial oligomerization of PrP106-126 are still obscure, which are very important for understanding the conformational conversion of PrP106-126. In this study, replica exchange molecular dynamics simulations were performed to investigate monomeric and dimeric states of PrP106-126 in implicit solvent. The structural diversity of PrP106-126 was observed and this peptide did not acquire stable structure. The dimeric PrP106-126 also displayed structural diversity and hydrophobic interaction drove the dimerization. To further study initial oligomerization of PrP106-126, 1 µs conventional molecular dynamics simulations of trimer and tetramer formation were carried out in implicit solvent. We have observed the spontaneous formation of several basic oligomers and stable oligomers with high β-sheet contents were sampled in the simulations of trimer and tetramer formation. The β-hairpin formed in hydrophobic tail of PrP106-126 with residues 118-120 in turn may stabilize these oligomers and seed the formation oligomers. This study can provide insight into the detailed information about the structure of PrP106-126 and the dynamics of aggregation of monomeric PrP106-126 into oligomers in atomic level.Lulu NingJingjing GuoQifeng BaiNengzhi JinHuanxiang LiuXiaojun YaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87266 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lulu Ning Jingjing Guo Qifeng Bai Nengzhi Jin Huanxiang Liu Xiaojun Yao Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
description	Prion diseases are marked by cerebral accumulation of the abnormal isoform of the prion protein. A fragment of prion protein composed of residues 106-126 (PrP106-126) exhibits similar properties to full length prion and plays a key role in the conformational conversion from cellular prion to its pathogenic pattern. Soluble oligomers of PrP106-126 have been proposed to be responsible for neurotoxicity. However, the monomeric conformational space and initial oligomerization of PrP106-126 are still obscure, which are very important for understanding the conformational conversion of PrP106-126. In this study, replica exchange molecular dynamics simulations were performed to investigate monomeric and dimeric states of PrP106-126 in implicit solvent. The structural diversity of PrP106-126 was observed and this peptide did not acquire stable structure. The dimeric PrP106-126 also displayed structural diversity and hydrophobic interaction drove the dimerization. To further study initial oligomerization of PrP106-126, 1 µs conventional molecular dynamics simulations of trimer and tetramer formation were carried out in implicit solvent. We have observed the spontaneous formation of several basic oligomers and stable oligomers with high β-sheet contents were sampled in the simulations of trimer and tetramer formation. The β-hairpin formed in hydrophobic tail of PrP106-126 with residues 118-120 in turn may stabilize these oligomers and seed the formation oligomers. This study can provide insight into the detailed information about the structure of PrP106-126 and the dynamics of aggregation of monomeric PrP106-126 into oligomers in atomic level.
format	article
author	Lulu Ning Jingjing Guo Qifeng Bai Nengzhi Jin Huanxiang Liu Xiaojun Yao
author_facet	Lulu Ning Jingjing Guo Qifeng Bai Nengzhi Jin Huanxiang Liu Xiaojun Yao
author_sort	Lulu Ning
title	Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
title_short	Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
title_full	Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
title_fullStr	Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
title_full_unstemmed	Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.
title_sort	structural diversity and initial oligomerization of prp106-126 studied by replica-exchange and conventional molecular dynamics simulations.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/65dcfc70056f434baecb14715d468476
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Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations.

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