Topomer CoMFA And Molecular Docking Study Of Anti-AIDS Drugs

Acquired immune deficiency syndrome?AIDS?was a fatal disease,which was caused by the human immunodeficiency virus?HIV?in humans.HIV can block the process of cellular and humoral immunity,the immune system was damaged,and then people was infected with HIV/AIDS.HIV password was expressed by three key enzymes which were HIV-1 Reverse transcriptase?RT??HIV-1 Protease?PR?and HIV-1 Integrase?IN?,as important enzymes,are important targets for the design of anti-AIDS drugs.There were two species of HIV which infect humans,namely HIV-1 and HIV-2,in which HIV-1 is more virulent because of it is easily transmitted.In this paper,the inhibitor was studied by computer aided drug design?CADD?,the quantitative structure-activity relationships?QSAR?study,molecular docking and molecular design,which provided theoretical for understanding of the action mechanism of drugs and the development of anti-AIDS drugs.The research content of this article is divided into the following several aspects parts as follows:1.Topomer CoMFA method was used to build a three-dimensional quantitative structure-activity relationship?3D-QSAR?model for 24 diarylaniline derivatives in this paper.The coefficient of non-cross validation?r²?,the coefficient of cross validation?q²?and external validation(Q_ext²)of good model were 0.928,0.654,and 0.940,respectively.The result showed that this model had a good stability and a predictive ability.By using molecular docking,the action mechanism of drug and acceptor was studied,and the results showed that the drug functions obviously with LYS172,GLU138,LYS101 sites of HIV-1reverse transcriptase.Based on the above informations,many new molecules of diarylaniline derivatives with high activity were designed,and the new inhibitors were docked into its targets using molecular docking to analyze their binding modes.2.Using Topomer CoMFA method,a good Topomer CoMFA model withpreferable stability and prediction abilities was built,and the relationships between dimensional structures and activities of 52 indole derivatives were studied.The coefficient of non-cross validation?r²?,the coefficient of cross validation?q²?and external validation(Q_ext²)of Topomer CoMFA model were0.996,0.651,and 0.764.Contour maps of Topomer CoMFA model provided visual field of electrostatic and steric field,it revealed that different substituent of compounds had effective biological activity.Based on the above informations,many new molecules of indole derivatives with high activity were theoretically designed.3.Topomer CoMFA method was used to build a 3D-QSAR model for 64 structurally diverse pyrimidine derivatives.and the coefficient of non-cross validation?r²?,the coefficient of cross validation?q²?and external validation(Q_ext²)of good model were 0.922?0.723 and 0.935.The result showed that this model had a good stability and a predictive ability.By using molecular docking,the action mechanism of drug and acceptor was studied,and the results showed that inhibitors and amino acid residues had hydrogen binding interaction.4.Using Topomer CoMFA and HQSAR two methods,QSAR models for 48 Quionolone caroxylic acid derivatives were built.The coefficient of non-cross validation?r²?,the coefficient of cross validation?q²?and external validation(Q_ext²)of two models were 0.967,0.775,0.915 and 0.967,0.796,0.955,respectively.The result showed that two models had a good stability and a predictive ability.Contour maps of Topomer CoMFA and color coding figures of HQSAR model revealed that different substituent of compounds have effective biological activity.By using molecular docking,the action mechanism of drug and acceptor was studied,and the results showed that the drug functions obviously with THR80?VAL82?GLY27?ASP29?ARG8 sites.5.Topomer CoMFA was used to build a 3D-QSAR model for 40 structurally diverse diaryltriazine?DATA?derivatives.The coefficient of non-cross validation?r²?,the coefficient of cross validation?q²?and external validation(Q_ext²)were 0.958?0.800 and 0.965.The result showed that this model had a good stability and a predictive ability.By using molecular docking,the action mechanism of drug and acceptor was studied,and the results showed that the drug and GLU138,LYS101,THR139 sites of HIV-1 reverse transcriptasehave obvious function,it could offer a theoretical reference for the pharmaceutical synthesis according to these results.