title: Docking and molecular dynamics studies of peripheral site ligand-oximes as reactivators of sarin-inhibited human acetylcholinesterase.
abstract: In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.
authors.affiliation: a Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD) , Military Institute of Engineering , Praça General Tibúrcio 80, 22290-270 Rio de Janeiro , Brazil.
authors.forename: Joyce S F D
authors.initials: JS
authors.lastname: de Almeida
authors.affiliation: a Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD) , Military Institute of Engineering , Praça General Tibúrcio 80, 22290-270 Rio de Janeiro , Brazil.|b Faculty of Technology , State University of Rio de Janeiro , Rod. Presidente Dutra Km 298, Pólo Industrial, 27537-000 Resende , RJ , Brazil.
authors.forename: Teobaldo R
authors.initials: TR
authors.lastname: Cuya Guizado
authors.affiliation: c Chemistry Department , Federal University of Viçosa , Avenida Peter Henry Rolfs, s/n-Campus Universitário, Zip CPO Box, Viçosa , MG , Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Guimarães
authors.affiliation: d Chemistry Department , Federal University of Lavras , PO Box 3037, 37200-000 Lavras , MG , Brazil.|g Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.affiliation: e Federal Institute of Education, Science and Technology , Avenida Ministro Salgado Filho, S/Nº - Bairro Soteco, Zip Code 29106-010 Vila Velha , Espírito Santo/ES , Brazil.
authors.forename: Arlan S
authors.initials: AS
authors.lastname: Gonçalves
authors.affiliation: f TNO Defense, Security & Safety , PO Box 45, 2280 AA Rijswijk , The Netherlands.
authors.forename: Martijn C
authors.initials: MC
authors.lastname: de Koning
authors.affiliation: a Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMACBD) , Military Institute of Engineering , Praça General Tibúrcio 80, 22290-270 Rio de Janeiro , Brazil.|g Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.|h Department of Chemistry and Biochemistry , Concordia University , 7141 Sherbrooke W, Montreal , Canada.
authors.forename: Tanos C C
authors.initials: TC
authors.lastname: França
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D012524:Sarin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D008024:Ligands; D010091:Oximes; D012524:Sarin; D000110:Acetylcholinesterase
keywords: acetylcholinesterase; nerve agents; oximes; peripheral site; reactivation