title: Ab initio molecular simulations for proposing potent inhibitors to butyrylcholinesterases.
abstract: Butyrylcholinesterase (BChE) exists mainly at neuromuscular junctions and plays an important role in the hydrolyzing mechanism of neurotransmitter acetylcholine. A variety of compounds have been produced in order to inhibit the function of BChE. We here investigate the specific interactions between BChE and some ligands (Kx) with large binding affinity to BChE, using ligand-docking, classical molecular mechanics and ab initio fragment molecular orbital (FMO) methods. The binding energies between BChE and Kx evaluated by the FMO method have a correlation with the 50% inhibition concentration obtained by the previous experiments. In addition, the FMO calculations highlight that Asp70, Trp82 and Tyr128 residues of BChE contribute significantly to the binding between BChE and Kx. Based on the results, we propose some novel ligands and elucidate that one of the proposed ligands can bind strongly to BChE. The present results are useful for developing potent inhibitors to BChE.
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Aichi 441-8580, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Murakawa
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Aichi 441-8580, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Aichi 441-8580, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Holmboevegen 3B, 9010 Tromsø, Norway.
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Aichi 441-8580, Japan. Electronic address: kurita@cs.tut.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
mesh_terms: D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation
chemical_list: D002800:Cholinesterase Inhibitors; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Butyrylcholinesterase; Inhibitors; Molecular docking; Molecular simulation; s