Molecule Design And Computer Simulation Of Small-Molecule Thrombin Inhibitor

Thromboembolic diseases are a leading cause of death in the world. The anticoagulant is used in prevention and treatment of thromboembolic disease via affecting the blood clotting process. Thrombin is a key enzyme of the coagulation process. Direct thrombin inhibitor directly interact with thrombin, cause the inactivation of thrombin.Recent research into active thrombin inhibitors is concentrated on derivatives based on the Original thrombin inhibitor. We designed27molecular based on the transformation of the P1, P2, P3sites of PPACK.Computer-aided drug design (CADD), refers to the use of computer calculations, logical judgments and graphic display and other functions, to establish the docking model of the drugs and the receptor, and calculate the bonding energy of the drug and receptor, which provide a guidance for rational drug design.We designed27molecular based on our previous work and document. The molecular docking software autodock4.2and MVD2010.4.0(Molegro Virtual Docker) were used to study the joint configuration between the inhibitors and the enzyme. In order to the docking result, five thrombin inhibitors of the27were synthesized and determined the actual inhibitory ratio.In order to the docking result, all the27compounds were able to combine with the active site of thrombin. but the docking energy are quite different. Contrast the autodock docking data with the MVD docking data, the docking results of the two software is basically same.Contrast the actual inhibitory ratio of the5compounds with the docking result, in order to the autodock docking data, moleculel,2,5showed higher activity, and In order to the MVD data, molecule1,2,3showed higher activity. The actual inhibitory ratio showed that molecule1,2,3,5were active. Based on the experiments, the computer simulation data is valuable.