Prediction of Molecular Interaction between Platelet Glycoprotein Ibα and von Willebrand Factor using Molecular Dynamics Simulations
Prediction of Molecular Interaction between Platelet Glycoprotein Ibα and von Willebrand Factor using Molecular Dynamics Simulations
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DOI：
10.5551/jat.32458
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发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Goto, Shinya
中科院分区：
文献类型：
--
作者：
Shiozaki, Seiji;Takagi, Shu;Goto, Shinya
目的：血小板膜糖蛋白Ibα(GPIBα)与血管性假血友病因子(VWF)在高剪切力作用下发生独特的相互作用，其分子机制尚不清楚。方法：采用NAMD(纳米分子动力学)程序包结合CHARMM 22(化学在哈佛大学大分子力学)力场进行分子动力学模拟，预测在水溶性条件下VWF A1结构域与GPIba N端区结合部位的动态结构变化。结果：预测稳定状态下VWF A1结构域与GPIba的平均质心距离为27.3埃。计算了不同质心距条件下VWF和GPIba的A1域间的平均力势。所有计算值均符合Morse势能函数曲线。通过对分子距离的平均作用力的求导，预测VWF A1结构域与GPIba之间的最大粘附力为62.3pN。结论：分子动力学模拟可用于预测参与血小板粘连的蛋白质键的动态结构变化，以及它们之间相互作用产生的粘附力。
Aim: The molecular mechanism of the unique interaction between platelet membrane glycoprotein Ib alpha (GPIb alpha) and von Willebrand Factor (VWF), necessary for platelet adhesion under high shear stress, is yet to be clarified.Methods: The molecular dynamics simulation using NAMD (Nanoscale Molecular Dynamics) package with the CHARMM 22 (Chemistry at Harvard Macromolecular Mechanics) force field were used to predict dynamic structural changes occurring in the binding site of A1 domain of VWF and N terminus domain of GPIba under water soluble condition.Results: The mean distance between the mass center of A1 domain of VWF and GPIba in the stable form was predicted as 27.3 angstrom. The potential of mean force between the A1 domain of VWF and GPIba were calculated in conditions of various distances of the mass center between them. All the calculated values were fitted to the Morse potential energy function curve. The maximum adhesive force between A1 domain of VWF and GPIba was predicted as 62.3 pN by differentiating the potential of mean force with respect to the molecular distance.Conclusions: The molecular dynamics simulation is useful for predicting the dynamic structure changes of protein bonds involved in platelet adhesion and for predicting the adhesive forces generated between their interactions.