The Application Of Computer-Aided Molecular Design In HIV-1and Gaucher Inhibitors

Quantitative structure-activity relationship (QSAR), molecular docking and molecular dynamics are important tools of computer-aided drug design (CADD). In this study, we aimed to HIV-1inhibitors and Gaucher inhibitors using of CADD to explore the influencing factors between the structures and activity and to explore the interaction between the drug and the protein.In the first part, chapter1reviewed those common methods and the theoretical backgrounds of QSAR, molecular docking and molecular dynamics. And then we described the procedure about the related software.The second part was divided into three chapters which were the practical application of HIV-1inhibitors and Gaucher disease inhibitors.The second and third chapters were aimed to the HIV-1inhibitors.3D-QSAR and molecular docking were used in the second chapter. We got the structural factors that governed the biological activity, and then we designed some new drugs based on the factors. We predicted the theoretical activity of new drugs, and calculated some chemical properties which could explain the stability of the new drugs. The new drugs’ activities, in theory, showed better than the original drugs’ biological activities. In the third chapter,3D-QSAR was used in derivatives of DCP and DCK of HIV-1, and offered information of structural factors that affected the activity. Molecular docking and molecular dynamics were applied to the structure which was highest activity to represent the flexibility and stability between the drugs and the protein.The forth chapter explored the inhibitors of Gaucher disease.2D-QSAR,3D-QSAR and molecular docking were carried out in this work. By means of molecular docking, we got the bioactive conformations of all compounds. We also could get the mode of interaction between the drugs and the protein via analysis of the energy which were produced in docking process. The descriptors of2D-QSAR and the contour maps of3D-QSAR not only illustrated the factors which infect the activity but also guided the new drugs’synthesis.