Different Physical Parameters in the Bonds between Platelet Glycoprotein Ibalpha with von Willebrand factor and with Coagulant Factor XI -Results from the Molecular Dynamic Simulation-

BackgroundBoth von Willebrand factor (VWF) and coagulation factor XI (FXI) bind with platelet membrane glycoprotein (GP) Ib. However, the differences in the physical parameters in the bonds between VWF-GPIb and FXI-GPIb mediating different biological functions are unclear. MethodsThe FXI molecule was arranged in 9 different initial positions around the structure of GPIb bound to VWF. The position coordinate and velocity vectors of all atoms constructing VWF, GPIb, and FXI were calculated in each 2 femto (10-15) second using the Chemistry at HARvard Macromolecular Mechanics (CHARMM) force field. The physical parameters of VWF-GPIb and FXI-GPIb bonds were calculated by molecular dynamic (MD) simulations. ResultsMD calculation revealed 2.8 to 11.3 times greater positional fluctuations in atoms constructing FXI-GPIb as compared to those constructing VWF-GPIb (RMSDs: 5.9{+/-}1.5 to 18.1{+/-}7.9 [A] for FXI-GPIb vs 1.6{+/-}0.1 to 2.1{+/-}0.3 [A] for VWF-GPIb). The absolute value of non-covalent binding energy generated in FXI-GPIb (65.5{+/-}79.7 to 517.6{+/-}54.2 kcal/mol) was smaller than that generated in VWF-GPIb (678.5{+/-}58.3 to 1000.4{+/-}75.1 kcal/mol). The binding structure of VWF-GPIb was stable and was only minimally influenced by the presence of FXI-GPIb binding. ConclusionsOur MD calculation results revealed that atoms constructing the VWF-GPIb bond are physically more stable and produce more non-covalent binding energy than the bond of FXI-GPIb. The physical parameters in the VWF-GPIb bond were not largely influenced by FXI binding with GPIb.