title: Computational studies of acetylcholinesterase complexed with fullerene derivatives: a new insight for Alzheimer disease treatment.
abstract: Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer's disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72, Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the drug design of new inhibitors of HssAChE based on C60 derivatives. Results presented here report for the first time by a new class of molecules that can become effective drugs against AD.
authors.affiliation: a Federal Institute of Education Science and Technology of Espirito Santo , unit Vila Velha, Avenida Ministro Salgado Filho, 1000, 29106-010 Soteco, Espírito Santo - ES , Brazil.
authors.forename: Arlan
authors.initials: A
authors.lastname: da Silva Gonçalves
authors.affiliation: b Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro, RJ , Brazil.|c Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.
authors.forename: Tanos Celmar Costa
authors.initials: TC
authors.lastname: França
authors.affiliation: a Federal Institute of Education Science and Technology of Espirito Santo , unit Vila Velha, Avenida Ministro Salgado Filho, 1000, 29106-010 Soteco, Espírito Santo - ES , Brazil.
authors.forename: Osmair
authors.initials: O
authors.lastname: Vital de Oliveira
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D037741:Fullerenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding
chemical_list: D002800:Cholinesterase Inhibitors; D037741:Fullerenes; D000110:Acetylcholinesterase; C069837:fullerene C60
keywords: AChE inhibition; Alzheimer’s disease; docking; fullerene derivatives; molecular modeling; theoretical methodologies