Molecular docking simulation studies suggest a new peptide inhibitor based on zymogen structure of trypsin from Periplaneta americana Blattodea: Blattidae
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عنوان دوره: سومین کنگره بین المللی حشره شناسی ایران
نویسندگان
Department of Plant Protection, College of Agriculture, Shahid Chamran University of Ahvaz, Ahvaz, Iran,
چکیده
Cockroaches consist of 4500 species, only a few of which are major domestic pests. They have associated with humans and have potential to transmit disease. Cockroach management is difficult to achieve using insecticides for numerous reasons, among which resistant to common compounds is the prevailed one. Recently, targeting digestive enzymes with proper inhibitors could be a novel alternative for chemical insecticides. Serine proteases like trypsin provide essential amino acids for insect pests through hydrolyzing ingested proteins and, therefore, they can affect the insect growth and development. Many proteases are released as inactive precursors or “zymogens” bearing the N-terminal proregions acting both as facilitating folding reactions and as inhibitors of proteolytic activity. The latter role of the proregions as potent and specific inhibitors of their related protease has been confirmed in different proteases and consequently has been targeted for alternative pest control. In this research, the amino acid sequences of P. americana midgut trypsin and its proregion were obtained from NCBI (accession number: AIA09342.1) and their binding affinity were evaluated in silico using computational modeling and docking simulations. At first, to understand some characteristic of P. americana trypsin, a reliable structural model of P. americana trypsin was constructed based on Rattus norvegicus trypsin crystal structure (PDB: 1CO7) using Modeller 9.21. Also, the structural model of peptideas inhibitor was predicted by I-TASSER server. Finally, docking simulation was conducted for prediction of the binding site and the potential of peptide inhibitor to block the key residues of P. americana trypsin via the robust modeling program HADDOCK. Cluster analysis of HADDOCK indicated that the peptide inhibitor could inhibit trypsin activity of P. americana with acceptable energy structure and binding affinity toward receptor binding site. These findings have revealed a valuable role of computational methods as a tool for the initial searching of a potent inhibitor originated from a proregion that is highly specific and selective to its mature enzyme. Our research could be a respectable starting point for future insecticide design
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