SMD Simulations of Shear Loading Induced Dissociation of P-selectin/PSGL-1 Complez
Selectin/ligand interactions mediate the tethering and rolling processes of blood cells on vascular surfaces. It has been demonstrated that flow is required during this adhesion process. But the molecular mechanism, e.g. how the shear loading from the hydrodynamic environment of the circulation influences the rupture of selectin/ligand complex, is still unclear. In this study, we simulated the dissociation process of P-selectin/PSGL-1 complex under shear loading at the atomic level. The shear field was established by stretching the top layer of water molecules using SMD method. The dynamic evolvement of microstructure of P-LE/SGP-3 complex, the minimal functional unit of Pselectin/ PSGL-1 complex, for different shear velocity was studied. The simulation results indicated that the extension in PLE occurred before the dissociation of P-LE/SGP-3 complex. During the dissociation process, two anti-parallel β-sheets in EGF and hydrogen bonds at the interface of EGF-Lec domains were broken, but the structure of Lec domain remained unchanged. Under the same initial inclination angle of molecular complex relative to flow direction, structural destruction time decreased but dissociation speed of the complex increased along with the increase of shear velocity. For the same shear velocity, the dissociation of the complex was speeded up when decreasing the initial inclination angle. This work provide a insight into understand the structural bases for the rupture of Pselectin/ PSGL-1 bond at atomic level.
SMD selectin adhesion molecular interaction
Peng Ren Shouqin Lü Yingyong Kang Bo Huo Mian Long
National Microgravity Laboratory and Center for Biomechanics and Bioengineering,Institute of Mechanics,Chinese Academy of Sciences,Beijing,China
国际会议
北京
英文
1-4
2009-06-11（万方平台首次上网日期，不代表论文的发表时间）