Towards quantum-based modeling of enzymatic reaction pathways: Application to the acetylholinesterase catalysis

• Published in: Chemical physics letters Vol. 556; pp. 251 - 255
• Main Authors: Polyakov, Igor V., Grigorenko, Bella L., Moskovsky, Alexander A., Pentkovski, Vladimir M., Nemukhin, Alexander V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 29.01.2013
• ISSN: 0009-2614; 1873-4448
• DOI: 10.1016/j.cplett.2012.11.021

[Display omitted] ► Acylation stage of acetylcholine hydrolysis by acetylcholinesterase was considered. ► Stability of the first tetrahedral intermediate consistent with experiments was confirmed. ► QM/MM and fragment molecular orbital approaches were applied. ► GAMESS(US) code operational on the ‘RSC Tornado’ computational cluster was used. We apply computational methods aiming to approach a full quantum mechanical treatment of chemical reactions in proteins. A combination of the quantum mechanical – molecular mechanical methodology for geometry optimization and the fragment molecular orbital approach for energy calculations is examined for an example of acetylcholinesterase catalysis. The codes based on the GAMESS(US) package operational on the ‘RSC Tornado’ computational cluster are applied to determine that the energy of the reaction intermediate upon hydrolysis of acetylcholine is lower than that of the enzyme–substrate complex. This conclusion is consistent with the experiments and it is free from the empirical force field contributions.