Study On Drug Molecular Design Of H5N1 Target

Chapter I: This paper introduces the commonly used methods and principles of molecular design of computer drugs,including quantitative structure-activity realtionship,molecular docking and density functional theory,introduces the structure and classification of the influenza virus,describe the structures and inhibitors of neuraminidase and hemagglutinin,respectively,and the status quo.Chapter II: The interaction of 22 zanamivir analogues with neuraminidase was studied,22 zanamivir analogs were docked with the receptor protein 3BEQ molecule to understand the pattern of interaction between them.Among them,the highest score of the No.21 molecule is 7.8939,and the molecule mainly acts through the ether bond,guanidine group and hydroxyl group through the hydrogen bond and the 3BEQ receptor.CoMFA model and CoMSIA model were established,q2 values were 0.599 and 0.592.The structure-activity relationship of the compounds was explained intuitively from the three-dimensional contour of the five fields(Steric,Electrostatic,Hydrophobic,Donor,Acceptor),explained the structural characteristics that affect the activity of the compounds,through the structural transformation of No.6 molecules,On this basis,designed seven new drug molecules.Chapter III: The docking of 32 oseltamivir analogues and 2HU4 molecules,to understand the interaction between them,in which the No.8 molecular docking score of up to 8.0967.Through the virtual screening method,the four molecules of ZINC85630415,ZINC85630440,ZINC85630532,ZINC85630579 were screened from the native product database to potentially inhibit PIC50 activity.CoMFA model and CoMSIA model were established,q2 values were 0.559 and 0.696.The structureactivity relationship of the compounds was explained intuitively from the threedimensional contour of the five fields,explained the structural characteristics that affect the activity of the compounds,through the structural transformation of No.22 molecules,On this basis,designed ten new drug molecules.Chapter IV: By docking 25 saponin derivatives with hemagglutinin receptor protein molecules(PDB code:2IBX),to understand the interaction between them,in which the No.4 molecular docking score of up to 5.9083.CoMFA model and CoMSIA model were established,q2 values were 0.559 and 0.696.The results of the analysis from five different fields explain the structural characteristics that affect the activityof the compound.Through the structural modification of the 22 th molecule and the design of 10 new drug molecules.Chapter V: Using density functional theory,using gaussion09 software,quantum chemical calculations were performed on neuraminidase inhibitors and hemagglutinin inhibitors,respectively,analyzed the differences between the design molecules and the original molecules from three aspects: geometric configuration,charge distribution and frontline molecular orbital,respectively,to find out the reasons for the difference in inhibitory activity.