VZL 2005, 74(5):165-171

Computer Modeling and Simulation - New Technologies in Development of Means against Combat Chemical Substances

Jiří Wiesner1, Zdeněk Kříž1, Kamil Kuča ORCID...2, Daniel Jun ORCID...2, Jaroslav Koča1
1 Masarykova univerzita, Národní centrum pro výzkum biomolekul Přírodovědecké fakulty, Brno
2 Univerzita obrany, katedra toxikologie Fakulty vojenského zdravotnictví v Hradci Králové

Reaktivace jako chemická reakce, při níž je inhibované serinové proteáze navrácena její katalytická účinnost, je známa již poměrně dlouho. Nicméně stále ještě nebyl nalezen reaktivátor, jež by byl schopen uspokojivě reaktivovat acetylcholinesterázu inhibovanou jakoukoli nervově paralytickou látkou (NPL), například sarinem, cyklosarinem, somanem, tabunem a VX. Pokusy nalézt takovou látku spočívaly do této chvíle jen v experimentálních metodách a strukturní aspekty reaktivace sledované počítačovými metodami doposud objasněny nebyly. V tomto případě se jedná o chemickou reakci, a to už samo o sobě vyžaduje použití pestré palety metod výpočetní chemie, aby mohly být vyřešeny jak strukturní, tak i energetické aspekty celého procesu.

Keywords: Acetylcholinesteráza; Reaktivace; Oximy; Molekulová dynamika; Docking; Kvantová chemie

Reactivation process, when catalytical potency to the inhibited serine protease is returned, has been known for a long time. Unfortunately, no single acetylcholinesterase (AChE) reactivator able to reactivate sufficiently AChE inhibited by all nerve agents (sarin, cyclosarin, soman, tabun or VX) has been used. Attempts to find such a compound were based on experimental methods only. However, structural aspects of reactivation examined by computer methods have not been explained till now. In this article, chemical reaction (reactivation) is described using the broad range of computer chemistry methods that is necessary for solving structural and energetical aspects of the whole process.

Keywords: Acetylcholinesterase; Reactivation; Oximes; Molecular dynamics; Docking; Quantum chemistry

Received: November 25, 2005; Published: December 1, 2005  Show citation

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Wiesner, J., Kříž, Z., Kuča, K., Jun, D., & Koča, J. (2005). Computer Modeling and Simulation - New Technologies in Development of Means against Combat Chemical Substances. Vojenské Zdravotnické Listy, 74(5-6), 165-171
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