Tabun is one of the most dangerous nerve agents because it has deleterious effects like inhibition of the essential enzymes acetylcholinesterase (AChE) and butyrylcholinesterase. Some oximes such HI6 as 2-PAM are nucleophiles that are capable to reactivate inhibited human AChE under some conditions. Zwitterionic and cationic species have the best chance of productive action on inhibited AChE. However uncharged oximes can give important interaction information. In order to investigate the interaction and behavior of cationic and uncharged oximes, we performed molecular docking simulations and molecular dynamics and calculated binding energies of complexes of these compounds with human AChE. The uncharged oximes of larger structure were more susceptible to the influence of the substituents on the phosphorus atom and presented low binding energies. In contrast, HI 6 and 2-PAM showed high binding energy values with great contribution of the amino acid Asp74, demonstrating the importance of the quaternary nitrogen to the affinity and interaction of the oximes/AChE tabun-inhibited complexes.
- Klíčová slova
- acetylcholinesterase, chemical defense, tabun, uncharged oximes,
- MeSH
- acetylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemie MeSH
- lidé MeSH
- organofosfáty chemie MeSH
- oximy chemie MeSH
- pralidoximové sloučeniny chemie MeSH
- reaktivátory cholinesterasy chemie MeSH
- simulace molekulového dockingu metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
- organofosfáty MeSH
- oximy MeSH
- pralidoxime MeSH Prohlížeč
- pralidoximové sloučeniny MeSH
- reaktivátory cholinesterasy MeSH
- tabun MeSH Prohlížeč
