On quantum mechanical--molecular mechanical (QM/MM) approaches to model hydrolysis of acetylcholine by acetylcholinesterase.
Chem Biol Interact
; 203(1): 51-6, 2013 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-22982775
ABSTRACT
We re-visited the results of quantum mechanics--molecular mechanics (QM/MM) approaches aiming to construct the reaction energy profile for the acylation stage of acetylcholine hydrolysis by acetylcholinesterase. The main emphasis of this study was on the energy of the first tetrahedral intermediate (TI) relative to the level of the enzyme-substrate (ES) complex for which contradictory data from different works had been reported. A new series of stationary points on the potential energy surface was calculated by using electronically embedding QM/MM schemes when starting from the crystal structure mimicking features of the reaction intermediate (PDB ID 2VJA). A thoughtful analysis allows us to conclude that the energy of TI should be lower than that of ES, and a proper treatment of contributions from the oxyanion hole residues accounts for their relative positions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
/
Acetilcolina
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
2013
Tipo de documento:
Article