CAS OpenIR  > 多相复杂系统国家重点实验室
Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha
Han, Mengzhi1,2; Xu, Ji1; Ren, Ying1; Li, Jinghai1
2016-02-01
Source PublicationBIOPHYSICAL CHEMISTRY
ISSN0301-4622
Volume209Issue:FEBPages:9-20
AbstractBinding 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.
KeywordGlycoprotein Ib Alpha Protein Conformational Transition Metadynamics Free Energy Landscape Molecular Dynamics
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
DOI10.1016/j.bpc.2015.11.002
Indexed BySCI
Language英语
WOS KeywordVON-WILLEBRAND-FACTOR ; MOLECULAR-DYNAMICS SIMULATIONS ; LINEAR CONSTRAINT SOLVER ; FREE-ENERGY LANDSCAPES ; INTRINSIC DISORDER ; TETHER BOND ; A1 DOMAIN ; HAIRPIN ; COMPLEX ; DISEASE
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Biophysics ; Chemistry, Physical
Funding OrganizationNational Natural Science Foundation of China(21103195 ; 91434104)
WOS IDWOS:000369462700002
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/20611
Collection多相复杂系统国家重点实验室
Affiliation1.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
Recommended Citation
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.
Files in This Item:
File Name/Size DocType Version Access License
Simulations of flow (2977KB)期刊论文出版稿限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Han, Mengzhi]'s Articles
[Xu, Ji]'s Articles
[Ren, Ying]'s Articles
Baidu academic
Similar articles in Baidu academic
[Han, Mengzhi]'s Articles
[Xu, Ji]'s Articles
[Ren, Ying]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Han, Mengzhi]'s Articles
[Xu, Ji]'s Articles
[Ren, Ying]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.