title: Prediction of Molecular Interaction between Platelet Glycoprotein Ibα and von Willebrand Factor using Molecular Dynamics Simulations.
abstract: OBJECTIVE
  The molecular mechanism of the unique interaction between platelet membrane glycoprotein Ibα (GPIbα) 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 GPIbα under water soluble condition.
  
  
  RESULTS
  The mean distance between the mass center of A1 domain of VWF and GPIbα in the stable form was predicted as 27.3 Å. The potential of mean force between the A1 domain of VWF and GPIbα 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 GPIbα 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.
authors.affiliation: Department of Medicine (Cardiology), Tokai University School of Medicine.
authors.forename: Seiji
authors.initials: S
authors.lastname: Shiozaki
authors.forename: Shu
authors.initials: S
authors.lastname: Takagi
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
mesh_terms: D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry*; D011485:Protein Binding; D000072417:Protein Domains; D033081:Shear Strength; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000737:chemistry*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor