In the present work, we performed a complementary quantum mechanical (QM) study to describe the mechanism by which deprotonated pralidoxime (2-PAM) could reactivate human (Homo sapiens sapiens) acetylcholinesterase (HssAChE) inhibited by the nerve agent VX. Such a reaction is proposed to occur in subsequent addition-elimination steps, starting with a nucleophile bimolecular substitution (SN2) mechanism through the formation of a trigonal bipyramidal transition state (TS). A near attack conformation (NAC), obtained in a former study using molecular mechanics (MM) calculations, was taken as a starting point for this project, where we described the possible formation of the TS. Together, this combined QM/MM study on AChE reactivation shows the feasibility of the reactivation occurring via attack of the deprotonated form of 2-PAM against the Ser203-VX adduct of HssAChE.

• Klíčová slova
• 2-PAM, QM/MM method, VX, acetylcholinesterase,
• MeSH
• acetylcholinesterasa chemie   účinky léků   MeSH
• katalytická doména MeSH
• kvantová teorie MeSH
• lidé MeSH
• molekulární konformace MeSH
• organothiofosforové sloučeniny farmakologie   MeSH
• pralidoximové sloučeniny chemie   farmakologie   MeSH
• protony MeSH
• serin chemie   MeSH
• simulace molekulární dynamiky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• organothiofosforové sloučeniny MeSH
• pralidoxime MeSH Prohlížeč
• pralidoximové sloučeniny MeSH
• protony MeSH
• serin MeSH
• VX MeSH Prohlížeč