Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha

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	Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha
	Han, Mengzhi 1,2; Xu, Ji 1; Ren, Ying 1; Li, Jinghai 1
刊名	BIOPHYSICAL CHEMISTRY
	2016-02-01
卷号	209 期号:FEB 页码:9-20
关键词	Glycoprotein Ib alpha Protein conformational transition Metadynamics Free energy landscape Molecular dynamics
ISSN号	0301-4622
英文摘要	Binding of glycoprotein Ib alpha to von Willebrand factor induces platelet adhesion to injured vessel walls and initiates a multistep hemostatic process. It has been hypothesized that the flow condition could induce a loop to beta-sheet conformational change in the beta-switch region of glycoprotein Ib alpha, which regulates it binding to the von Willebrand factor and facilitates the blood clot formation and wound healing. In this work, direct molecular dynamics (MD), flow MD and metadynamics, were employed to investigate the mechanisms of this flow induced conformational transition process. Specifically, the free energy landscape of the whole transition process was drawn by metadynamics with the path collective variable approach. The results reveal that without flow, the free energy landscape has two main basins, including a random loop basin stabilized by large conformational entropy and a partially folded beta-sheet basin. The free energy barrier separating these two basins is relatively high and the beta-switch could not fold from loop to beta-sheet state spontaneously. The fully beta-sheet conformations located in high free energy regions, which are also unstable and gradually unfold into partially folded beta-sheet state with flow. Relatively weak flow could trigger some folding of the beta-switch but could not fold it into fully beta-sheet state. Under strong flow conditions, the beta-switch could readily overcome the high free energy barrier and fold into fully beta-sheet state. (C) 201 5 Elsevier B.V. All rights reserved.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
类目[WOS]	Biochemistry & Molecular Biology ; Biophysics ; Chemistry, Physical
研究领域[WOS]	Biochemistry & Molecular Biology ; Biophysics ; Chemistry
关键词[WOS]	VON-WILLEBRAND-FACTOR ; MOLECULAR-DYNAMICS SIMULATIONS ; LINEAR CONSTRAINT SOLVER ; FREE-ENERGY LANDSCAPES ; INTRINSIC DISORDER ; TETHER BOND ; A1 DOMAIN ; HAIRPIN ; COMPLEX ; DISEASE
收录类别	SCI
语种	英语
WOS记录号	WOS:000369462700002
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/20611]
专题	过程工程研究所_多相复杂系统国家重点实验室
作者单位	1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Multiphase Complex Syst, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Han, Mengzhi,Xu, Ji,Ren, Ying,et al. Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha[J]. BIOPHYSICAL CHEMISTRY,2016,209(FEB):9-20.
APA	Han, Mengzhi,Xu, Ji,Ren, Ying,&Li, Jinghai.(2016).Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha.BIOPHYSICAL CHEMISTRY,209(FEB),9-20.
MLA	Han, Mengzhi,et al."Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha".BIOPHYSICAL CHEMISTRY 209.FEB(2016):9-20.