Molecular Dynamics Simulation Study of the Selective Inhibition of Coagulation Factor IXa over Factor Xa.

Thromboembolic disorders, arising from abnormal coagulation, pose a significant risk to human life in the modern world. The FDA has recently approved several anticoagulant drugs targeting factor Xa (FXa) to manage these disorders. However, these drugs have potential side effects, leading to bleeding complications in patients.

A Structure Based Study of Selective Inhibition of Factor IXa over Factor Xa.

Blood coagulation is an essential physiological process for hemostasis; however, abnormal coagulation can lead to various potentially fatal disorders, generally known as thromboembolic disorders, which are a major cause of mortality in the modern world. Recently, the FDA has approved several anticoagulant drugs for Factor Xa (FXa) which work via the common pathway of the coagulation cascade. A main side effect of these drugs is the potential risk for bleeding in patients.

Automatic domain decomposition of proteins by a Gaussian Network Model.

Proteins are often comprised of domains of apparently independent folding units. These domains can be defined in various ways, but one useful definition divides the protein into substructures that seem to move more or less independently. The same methods that allow fairly accurate calculation of motion can be used to help classify these substructures.

Molecular mechanism of domain swapping in proteins: an analysis of slower motions.

Domain swapping is a structural phenomenon that plays an important role in the mechanism of oligomerization of some proteins. The monomer units in the oligomeric structure become entangled with each other. Here we investigate the mechanism of domain swapping in diphtheria toxin and the structural criteria required for it to occur by analyzing the slower modes of motion with elastic network models, Gaussian network model and anisotropic network model.

Dynamics of proteins in crystals: comparison of experiment with simple models.

The dynamic behavior of proteins in crystals is examined by comparing theory and experiments. The Gaussian network model (GNM) and a simplified version of the crystallographic translation libration screw (TLS) model are used to calculate mean square fluctuations of C(alpha) atoms for a set of 113 proteins whose structures have been determined by x-ray crystallography. Correlation coefficients between the theoretical estimations and experiment are calculated and compared.