Seiji Shiozaki

Development of Virtual Platelets Implementing the Functions of Three Platelet Membrane Proteins with Different Adhesive Characteristics

AIM Computer simulation is a new method for understanding biological phenomena. In this report, we developed a simple platelet simulator representing platelet adhesion under blood flow conditions. METHODS We generated virtual platelets based on the functions of three key adhesive proteins: glycoprotein (GP) Ibα, GPIIb/IIIa and collagen receptors. The adhesive force between GPIbα and von Willebrand factor (VWF) was set to increase in association with increments in the fluid shear stress. GPIIb/IIIa acquires an adhesive force to bind with ligands only when platelets are activated following multiple GPIbα stimulation by VWF or collagen receptors. RESULTS Upon perfusion over the area of virtual endothelial injury, the virtual platelets adhered and became activated to form platelet thrombi. A total of 286/mm(2) of activated platelets was found to have accumulated downstream of the flow obstacle within 30 seconds, with 59/mm(2) platelets adhering upstream. The results obtained with the virtual model were consistent with those for real platelets in human blood in the presence of similarly shaped flow obstacles. CONCLUSIONS Our computer platelet simulator, which employs the functions of three key platelet membrane proteins, shows similar findings for adhesion in the presence and absence of blood flow obstacles.

Prediction of Molecular Interaction between Platelet Glycoprotein Ibα and von Willebrand Factor using Molecular Dynamics Simulations

AIM 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.

Multiscale Analysis of Heterogeneous Catalysis on a Silica Surface

Many studies have been reported about the catalytic recombination of oxygen and nitrogen on a silica surface, which is quite important for the reentry of a space vehicle. But, the reaction mechanism is not fully understood. Hence, in this study, we are constructing a catalytic reaction model using the ab initio calculations and the Monte Carlo calculations in order to reveal the reaction mechanism. First, desorption and surface migration of oxygen atoms on the α-quartz (0001) reconstructed surface were investigated using density functional theory. The result indicates that Langmuir-Hinshelwood (L-H) recombination frequently occurs at high temperature. Then detailed analysis of L-H mechanism was performed and the rate controlling factor was discussed.