首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Dynamic structure based pharmacophore modeling of the Acetylcholinesterase reveals several potential inhibitors
Authors:Fereshteh Shiri  Somayeh Pirhadi  Jahan B Ghasemi
Institution:1. Department of Chemistry, University of Zabol , Zabol, Iran;2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences , Shiraz, Iran;3. School of Chemistry, University College of Science, University of Tehran , Tehran, Iran
Abstract:Acetylcholinesterase is a critical enzyme that regulates neurotransmission by catalyzing the breakdown of neurotransmitter acetylcholine in synapses of the nervous system. It is an important target for therapeutic drugs that treat Alzheimer’s disease. Since, the degree of flexibility of the side chains of the residues in the active-site gorge of Acetylcholinesterase is diverse it results in different bound ligand conformations. The side-chain conformations of Ser293, Tyr341, Leu76, and Val73 are flexible, while the side-chain conformations of Tyr72, Tyr 124, Ser125, Phe295, and Arg296 appear to be fixed. In this study, multi-conformation dynamic pharmacophore models from the donepezyl-binding pocket based on highly populated structures chosen from molecular dynamics simulations were used for screening compounds that can properly bind acetylcholinesterase. Based on these structures, three pharmacophore models were generated. Consequently, 14 hits were retrieved as final candidates by utilizing virtual screening of ZINC database and molecular docking.
Keywords:Acetylcholinesterase  pharmacophore  shape filter  virtual screening  Alzheimer’s disease
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号