Virtual Screening Of Trehalose Enzymes Inhibitor And Theoretical Evaluation

With the progress of agricultural modernization, the application of artificial synthesized pesticide in prevention and cure of plant diseases and insect pests have become an important approach to improve the yield of crops. To overcome the negative effects of traditional chemical pesticides, such as pesticide residues and drug-fast of insects, development of novel pollution-less biological pesticides has become a new research filed. Advances of biological technology, especially the emergence of cheminformatics and the application of computer-aided drug design theory, provide an unprecedented opportunity for this research work.In recent years, the substrates used by insects as energy sources in the process of metabolism, such as Trehalose, Chitin, Growth Hormone, have been studied for their potency as new target of pesticide. Trehalose as the main matter of energy source in the insects' flight, broadly exists in different sorts of insects, and plays an important role in the energy metabolism. Therefore, taking Trehalose Enzymes as a target of pesticide to disturb the function of Trehalose in the metabolism for sake of killing insects has become a new way of pesticide research.Studies relating to the function of trehalose in the insects body are carried out in the present study. Via analyzing sequences of trehalose synthetase from GenBank database and referring to reports of inhibitors of trehalase of recent years, the possibility of Trehalose Enzymes as new targets of pesticide has been explored by using of computer-added drug design software. The main points of this dissertation are as follows:1, Gene-fusion has occurred in the long history of evolution for Trehalose synthetase of invertebrates. The coding genes for trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase have connected together by an intron.2 By Homology Modeling, 3D structures of trehalose synthetase has been constructed firstly, and structure reasonability assessment showed that structures of CG4104-PA(A) and CG4104-PA(B) are all reasonable conformations. The docking results of CG4104-PA(A) with ligands provide us geometric position information of ligand in different allowed low energy conformations. These results have directive significance for the research and development of trehalose synthetase inhibitors.3 Based on the gained molecular structure information of trehalase inhibitors, incorporating the molecular superposition result from Sybyl7.0/Gasp software, series of key functional groups in ligand structures related to the interaction with receptors have been determined and been used as query structures for pharmacophore-based database searching. 139 small molecule structures are found, from which 20 proper ones are selected for analysis of toxicity and security in aid of Tupcat7.0 software. The results will provide some new clues for the following studies.