Reactivation of VX-Inhibited Human Acetylcholinesterase by Deprotonated Pralidoxime. A Complementary Quantum Mechanical Study

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 2; p. 192
• Main Authors: da Silva, Jorge Alberto Valle, Pereira, Ander Francisco, LaPlante, Steven R, Kuca, Kamil, Ramalho, Teodorico Castro, França, Tanos Celmar Costa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 27.01.2020; MDPI AG
• Subjects: 2-pam; Acetylcholinesterase; Acetylcholinesterase - chemistry; Acetylcholinesterase - drug effects; Catalytic Domain; Humans; Life Sciences; Molecular Conformation; Molecular Dynamics Simulation; Organothiophosphorus Compounds; Organothiophosphorus Compounds - pharmacology; Pralidoxime Compounds; Pralidoxime Compounds - chemistry; Pralidoxime Compounds - pharmacology; Protons; qm/mm method; Quantum Theory; Serine; Serine - chemistry; QM/MM method; acetylcholinesterase; VX; 2-PAM

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 ( ) acetylcholinesterase ( AChE) inhibited by the nerve agent VX. Such a reaction is proposed to occur in subsequent addition-eli...