We investigated the solution structure and dynamics of the human anti-coagulation protein Z (PZ) in the complex with protein Zdependent protease inhibitor (ZPI) to order to understand key structural changes in the presence and absence of Ca(2+). Structural features of the complete complex of PZ-ZPI are poorly understood due to lack of complete atomic model of the PZ-ZPI complex. We have constructed a model of the complete PZ-ZPI complex and molecular dynamics (MD) simulation of the solvated PZ-ZPI complex with and without Ca(2+) was achieved for 100ns. It is consider that the Ω-loop of GLA domains interacts with negatively charged biological membranes in the presence of Ca(2+) ions. The PZ exerts its role as cofactor in a similar way. However, we used solvent-equilibrated dynamics to show structural features of the PZ-ZPI complex in the presence and the absence of Ca(2+)ions. We observed that the distance between the interacting sites of the ZPI with the PZ and the GLA domain decreases in the presence of Ca(2+) ions. Further, we postulated that the calculated distance between the dominant plane of the Ca(2+) ions and Ser196 of the pseudo-catalytic triad of the PZ is similar to the equivalent distance of FXa. This suggests that the central role of the PZ in the blood coagulation may be to align the inhibitory site of the ZPI with the active site of the FXa, which is depends on the interaction of the calcium bound GLA domain of the PZ with the active membrane.
Keywords: Blood coagulation; Ca ion; Molecular Dynamics simulation; Protein Z; Protein Z-dependent protease inhibitor.