Perera L, Darden T A, Pedersen L G
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
Biophys J. 1999 Jul;77(1):99-113. doi: 10.1016/S0006-3495(99)76875-X.
The crystallographic structure of human coagulation factor VIIa/tissue factor complex bound with calcium ions was used to model the solution structure of the light chain of factor VIIa (residues 1-142) in the absence of tissue factor. The Amber force field in conjunction with the particle mesh Ewald summation method to accommodate long-range electrostatic interactions was used in the trajectory calculations. The estimated TF-free solution structure was then compared with the crystal structure of factor VIIa/tissue factor complex to estimate the restructuring of factor VIIa due to tissue factor binding. The solution structure of the light chain of factor VIIa in the absence of tissue factor is predicted to be an extended domain structure similar to that of the tissue factor-bound crystal. Removal of the EGF1-bound calcium ion is shown by simulation to lead to minor structural changes within the EGF1 domain, but also leads to substantial relative reorientation of the Gla and EGF1 domains.
结合钙离子的人凝血因子VIIa/组织因子复合物的晶体结构被用于模拟在没有组织因子的情况下因子VIIa轻链(残基1 - 142)的溶液结构。在轨迹计算中使用了Amber力场并结合粒子网格埃瓦尔德求和方法来处理长程静电相互作用。然后将估计的无组织因子溶液结构与因子VIIa/组织因子复合物的晶体结构进行比较,以评估由于组织因子结合导致的因子VIIa的结构重组。预计在没有组织因子的情况下因子VIIa轻链的溶液结构是一种延伸的结构域结构,类似于与组织因子结合的晶体结构。模拟显示去除与EGF1结合的钙离子会导致EGF1结构域内的微小结构变化,但也会导致Gla和EGF1结构域的显著相对重新定向。