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2.  A Revisit to the One Form Kinetic Model of Prothrombinase 
Biophysical chemistry  2010;149(1-2):28-33.
Thrombin is generated enzymatically from prothrombin by two pathways with the intermediates of meizothrombin and prethrombin-2. Experimental concentration profiles from two independent groups for these two pathways have been re-analyzed. By rationally combining the independent data sets, a simple mechanism can be established and rate constants determined. A structural model is consistent with the data-derived finding that mechanisms that feature channeling or ratcheting are not necessary to describe thrombin production.
PMCID: PMC2877601  PMID: 20435402
enzyme kinetics; molecular dynamics simulation; blood coagulation
3.  Recent Estimates of the Structure of the Factor VIIa (FVIIa)/Tissue Factor (TF) and Factor Xa (FXa) Ternary Complex 
Thrombosis research  2010;125S1:S7-S10.
The putative structure of the Tissue Factor/Factor VIIa/Factor Xa (TF/FVIIa/FXa) ternary complex is reconsidered. Two independently derived docking models proposed in 2003 (one for our laboratory: CHeA and one from the Scripps laboratory: Ss) are dynamically equilibrated for over 10 ns in an electrically neutral solution using all-atom molecular dynamics. Although the dynamical models (CHeB and Se) differ in atomic detail, there are similarities in that TF is found to interact with the γ-carboxyglutamic acid (Gla) and Epidermal Growth Factor-like 1 (EGF-1) domains of FXa, and FVIIa is found to interact with the Gla, EGF-2 and serine protease (SP) domains of FXa in both models. FVIIa does not interact with the FXa EGF-1 domain in Se and the EGF domains of FVIIa do not interact with FXa in the CHeB. Both models are consistent with experimentally suggested contacts between the SP domain of FVIIa with the EGF-2 and SP domains of FXa.
PMCID: PMC2839023  PMID: 20156644
Factor VIIa; Factor Xa; ternary complex; Molecular Dynamics simulation
4.  Conformational change path between closed and open forms of C2 domain of coagulation factor V on a two-dimensional free-energy surface 
We test a hypothesis that the closed form of the C2 domain of coagulation factor V is more stable than the open form in an aqueous environment using a two-dimensional free-energy calculation with a simple dielectric solvent model. Our result shows that while the free-energy difference between two forms is small, favoring the closed form, a two-dimensional free-energy surface (FES) reveals that a transition state (1.53 kcal/mol) exists between the two conformations. By mapping the one-dimensional order parameter ΔQ onto the two-dimensional FES, we search the conformational change path with the highest Boltzmann weighting factor between the closed and open form of the factor V C2 domain. The predicted transition path from the closed to open form is not that of simple side chain movements, but instead concerted movements of several loops. We also present a one-dimensional free-energy profile using a collective order parameter, which in a coarse manner locates the energy barriers found on the two-dimensional FES.
PMCID: PMC2746997  PMID: 19518258
5.  A computational modeling and molecular dynamics study of the Michaelis complex of human protein Z-dependent protease inhibitor (ZPI) and factor Xa (FXa) 
Journal of molecular modeling  2009;15(8):897-911.
Protein Z-dependent protease inhibitor (ZPI) and antithrombin III (AT3) are members of the serpin superfamily of protease inhibitors that inhibit factor Xa (FXa) and other proteases in the coagulation pathway. While experimental structural information is available for the interaction of AT3 with FXa, at present there is no structural data regarding the interaction of ZPI with FXa, and the precise role of this interaction in the blood coagulation pathway is poorly understood. In an effort to gain a structural understanding of this system, we have built a solvent equilibrated three-dimensional structural model of the Michaelis complex of human ZPI/FXa using homology modeling, protein–protein docking and molecular dynamics simulation methods. Preliminary analysis of interactions at the complex interface from our simulations suggests that the interactions of the reactive center loop (RCL) and the exosite surface of ZPI with FXa are similar to those observed from X-ray crystal structure-based simulations of AT3/FXa. However, detailed comparison of our modeled structure of ZPI/FXa with that of AT3/FXa points to differences in interaction specificity at the reactive center and in the stability of the inhibitory complex, due to the presence of a tyrosine residue at the P1 position in ZPI, instead of the P1 arginine residue in AT3. The modeled structure also shows specific structural differences between AT3 and ZPI in the heparin-binding and flexible N-terminal tail regions. Our structural model of ZPI/FXa is also compatible with available experimental information regarding the importance for the inhibitory action of certain basic residues in FXa.
PMCID: PMC2723763  PMID: 19172319
Antithrombin III; Factor Xa; Homology modeling; Molecular dynamics simulation; Protein-protein docking; Protein Z-dependent protease inhibitor; Reactive center loop; Serpins
6.  Tuberculous Aneurysm of the Abdominal Aorta: Endovascular Repair Using Stent Grafts in Two Cases 
Korean Journal of Radiology  2000;1(4):215-218.
Tuberculous aneurysm of the aorta is exceedingly rare. To date, the standard therapy for mycotic aneurysm of the abdominal aorta has been surgery involving in-situ graft placement or extra-anatomic bypass surgery followed by effective anti-tuberculous medication. Only recently has the use of a stent graft in the treatment of tuberculous aortic aneurysm been described in the literature. We report two cases in which a tuberculous aneurysm of the abdominal aorta was successfully repaired using endovascular stent grafts. One case involved is a 42-year-old woman with a large suprarenal abdominal aortic aneurysm and a right psoas abscess, and the other, a 41-year-old man in whom an abdominal aortic aneurysm ruptured during surgical drainage of a psoas abscess.
PMCID: PMC2718204  PMID: 11752958
Aorta, disease; Aorta, aneurysm; Aorta, grafts and prostheses

Results 1-6 (6)