Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun conjugate: a molecular modeling approach

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F17%3A50013963" target="_blank" >RIV/62690094:18450/17:50013963 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10374724

Výsledek na webu

<a href="http://dx.doi.org/10.1080/07391102.2017.1324322" target="_blank" >http://dx.doi.org/10.1080/07391102.2017.1324322</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2017.1324322" target="_blank" >10.1080/07391102.2017.1324322</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun conjugate: a molecular modeling approach

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun conjugate: a molecular modeling approach

Popis výsledku anglicky

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.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA15-16701S" target="_blank" >GA15-16701S: Koncept nekvarterních reaktivátorů AChE jakožto antidot otrav organofosfáty - nová naděje či slepá cesta?</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of biomolecular structure and dynamics

ISSN

0739-1102

e-ISSN

—

Svazek periodika

Neuveden

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1-9

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85019565595