Free energies and folding mechanics between human prion fragment α-2 domain and β-2 domain under steered molecular dynamics simulations

doi:10.1016/j.jtice.2011.03.003

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Title:	Free energies and folding mechanics between human prion fragment α-2 domain and β-2 domain under steered molecular dynamics simulations
Authors:	Wang, Yeng-Tseng Su, Zhi-Yuan
Contributors:	資訊管理系
Keywords:	Prion β –sheet Prion α-helix 2 Molecular dynamics Folding mechanics
Date:	2011-09
Issue Date:	2013-09-28 16:25:37 (UTC+8)
Publisher:	Elsevier
Abstract:	Prion proteins are associated with a group of transmissible neurodegenerative disorders such as scrapie in sheep and Creutzfeldt–Jakob disease in humans. Previous studies have shown that the C-terminal side of α-helix 2 of the prion protein undergoes a conformational change to the β-sheet form, which is the infectious isoform causing scrapie. However, information about the three-dimensional structure of the prion β-sheet is still lacking. As the α-helix 2 displays “chameleon” conformational behavior, gathering several disease-associated point mutations, it can be toxic to neuronal cells. This makes it a very important focus for research into the folding mechanics of PrPC. The purpose of this study was to investigate the differences in folding mechanics between prion fragment α-helix 2 and prion fragment β-sheet 2, and to use a steered molecular dynamics approach to infer which events are important to achieve a normal α-helix 2 peptide. Based on our simulations, we suggest that 2 conformational barriers, comprising 4 intramolecular hydrogen bonds (the 8th, 9th, 10th, and 11th) and 6 residues (Thr183, Ile184, Lys185, His187, Thr188, and Val189), might play important roles in the folding mechanics of α-helix 2 and that a lack of these events might cause its misfolding. Steered molecular dynamics simulations were carried out on the folding mechanics of protein α-helix 2. The hypothesis we propose is that 6 residues (Thr183, Ile184, Lys185, His187, Thr188, and Val189) are important in the correct folding of prion α-helix 2
Relation:	Journal of the Taiwan Institute of Chemical Engineers 42(5), pp.719-723
Appears in Collections:	[Dept. of Information Management] Periodical Articles

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