期刊论文详细信息
Polymers | |
Exposure of Von Willebrand Factor Cleavage Site in A1A2A3-Fragment under Extreme Hydrodynamic Shear | |
Simone Melchionna1  Aleksey V. Belyaev2  Daria O. Yurkova2  Emeline Laborie3  Philippe Derreumaux3  Olivier Languin-Cattoën3  Fabio Sterpone3  | |
[1]Dipartimento di Fisica, Università Sapienza, P.le A. Moro 5, 00185 Rome, Italy | |
[2]Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia | |
[3]Laboratoire de Biochimie Théorique, CNRS, Université de Paris, UPR 9080, 13 rue Pierre et Marie Curie, F-75005 Paris, France | |
关键词: von Willebrand factor; molecular dynamics; coarse-grains; lattice Boltzmann; shear flow; protein unfolding; | |
DOI : 10.3390/polym13223912 | |
来源: DOAJ |
【 摘 要 】
Von Willebrand Factor (vWf) is a giant multimeric extracellular blood plasma involved in hemostasis. In this work we present multi-scale simulations of its three-domains fragment A1A2A3. These three domains are essential for the functional regulation of vWf. Namely the A2 domain hosts the site where the protease ADAMTS13 cleavages the multimeric vWf allowing for its length control that prevents thrombotic conditions. The exposure of the cleavage site follows the elongation/unfolding of the domain that is caused by an increased shear stress in blood. By deploying Lattice Boltzmann molecular dynamics simulations based on the OPEP coarse-grained model for proteins, we investigated at molecular level the unfolding of the A2 domain under the action of a perturbing shear flow. We described the structural steps of this unfolding that mainly concerns the【 授权许可】
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