Molecular Simulation And QSAR Study Drug Interaction Between Ligands And Their Receptors

In this paper, the methods of molecular docking and quantitative structure-activity relationship(QSAR) were introduced to study the mechanism of interaction between progesterones and PR/SHBG receptors and between Cinnamamides and HDAC1 receptor. This thesis mainly divided into the following four parts:In the first part, a brief introduction about the theories of molecular docking、quantitative structure-activity relationship(QSAR)and the used softweres were Provided in paper. Then a review about the research progess of progesterone derivatives and cinnamon amide derivatives was given.In the second part, the methods of molecular docking and QSAR were applied to study the mechanism of interaction of progesterone derivatives with PR and HSBG receptors. The docking and QSAR resultsshow that the main interaction forces of binding are hydrogen bonding force and Van der Walls force in the binding process of progesterone derivatives with PR and HSBG receptors. The quantitative structure–activity relationship models have been built between Progesterones and PR and between Preogesterones and SHBG, the values of R is 0.95, 0.92 respectively. By analysising the two results, it can be found that the influences of hydrogen bonding force, Van der Walls force and electrostatic effect have a difference in Progesterones-PR and Preogesterones-SHBG. These results may provide a useful guide for designing new highly active Preogesterones.In the third part, the HDAC1 protein was builded by Homology Modeling. Then, the methods of molecular docking and QSAR were applied to study the mechanism of interaction between Cinnamamide derivatives and HDAC1 receptors. The docking and QSAR results showed that the main interaction forces of binding were hydrogen bonding force and Van der Walls force, and the best model’s vaule of R is0.88. Lastly, we used the bulided QSAR model to prdicted the nine new compounds. The predicted result can guide us to further study about cinnamon amide compounds.In the fourth part, a summary for this paper was given, and the future direction of this work was also pointed out in the end.