title: Potential acetylcholinesterase inhibitors: molecular docking, molecular dynamics, and in silico prediction.
abstract: This paper deals with molecular modeling of new therapeutic agents for treating the Alzheimer's disease. The therapeutic line adopted for this study is the cholinergic hypothesis. To modulate positively the cholinergic function through the inhibition of the acetylcholinesterase, a set of candidates was designed from a natural compound extracted from the cashew nutshell liquid, anacardic acid. In silico screening of this chemical library revealed a ligand that is more promising once it is correlated with an active drug through specific topological and electronic descriptors. The protein-ligand docking showed stable binding modes and the binding free energy computed for the active site of the receptor suggests that our ligand presents a potential biological response. Graphical Abstract Representation of the three dimensional structure of the AChE, showing the important binding sites of the Gorge and the conformation of the ligand.
authors.affiliation: Institute of Biology, University of Brasilia, Brasilia, Brazil.
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Kiametis
authors.affiliation: Institute of Physics, University of Brasilia, Brasilia, Brazil. abreu_monica@yahoo.com.br.
authors.forename: Mônica A
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Departament of Tropical Medicine, University of Brasilia, Brasilia, Brazil.
authors.forename: Luiz A S
authors.initials: LA
authors.lastname: Romeiro
authors.affiliation: Institute of Chemistry, University of Brasilia, Brasilia, Brazil.
authors.forename: João B L
authors.initials: JB
authors.lastname: Martins
authors.affiliation: Institute of Physics, University of Brasilia, Brasilia, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gargano
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000544:Alzheimer Disease / Q000188:drug therapy*; D048729:Anacardic Acids / Q000737:chemistry; D031021:Anacardium / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation
chemical_list: D048729:Anacardic Acids; D002800:Cholinesterase Inhibitors; C088115:anacardic acid; D000110:Acetylcholinesterase
keywords: AChE inhibitors design; In silico prediction; Molecular docking; Molecular dynamics