Molecular dynamics simulations and QM/MM studies of the reactivation by 2-PAM of tabun inhibited human acethylcolinesterase

Journal of the Brazilian Chemical Society

França, Tanos C. C.¹  Instituto Militar de Engenharia, Rio de Janeiro, Brazil¹  Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil¹  Figueroa-Villar, José D.¹  Gonçalves, Arlan da Silva¹  Pascutti, Pedro G.¹ 

关键词: QM/MM studies;    acethylcolinesterase;    molecular dynamics;    pralidoxime;   

DOI  :  10.1590/S0103-50532011000100021

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

The elucidation of the reactivation routes of human acetylcholinesterase (HuAChE) inhibited by organophosphorous compounds is of crucial importance to the development of efficient antidotes against poisoning by chemical warfare agents. In order to contribute to a better understanding of the reactivation mechanism, we applied, in this work, classical molecular dynamics (MD) simulations to study the interactions between pralidoxime and the active site's amino acids of HuAChE inhibited by the neurotoxic agent tabun. Further, quantum mechanical/molecular mechanical (QM/MM) hybrid methods were used to propose a reactivation mechanism for the inhibited enzyme. The results showed that the classic MD kept pralidoxime inside the enzyme's active site, in a favorable region to the occurrence of possible reactions of dephosphorilation, which were confirmed by QM/MM methods, and lead to the proposition of an energetically favorable mechanism of reactivation.

【 授权许可】

Unknown