Quantum mechanics and mixed quantum mechanics/molecular mechanics simulations of model nerve agents with acetylcholinesterase |
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Authors: | MM Hurley JB Wright GH Lushington WE White |
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Institution: | (1) US Army Research Laboratory, AMSRL-CI-HC, Aberdeen Proving Ground, MD 21005, USA, US;(2) US Army Natick Soldier Center, AMSSB-RSS-M, Kansas St., Natick, MA 01760, USA, US;(3) University of Kansas, 1251 Wescoe Hall Rd., c/o Dept. of Medicinal Chemistry, Lawrence, KS 66045, USA, US;(4) Edgewood Chemical Biological Center, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010, USA, US |
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Abstract: | The accurate modeling of biological processes presents major computational difficulties owing to the inherent complexity
of the macromolecular systems of interest. Simulations of biochemical reactivity tend to require highly computationally intensive
quantum mechanical methods, but localized chemical effects tend to depend significantly on properties of the extended biological
environment – a regime far more readily examined with lower-level classical empirical models. Mixed quantum/classical techniques
are gaining in popularity as a means of bridging these competing requirements. Here we present results comparing two quantum
mechanics/molecular mechanics implementations (the SIMOMM technique of Gordon et al. as implemented in GAMESS, and the ONIOM
technique of Morokuma et al. found in Gaussian 98) as performed on the enzyme acetylcholinesterase and model nerve agents.
This work represents part of the initial phase of a DoD HPCMP Challenge project in which we are attempting to reliably characterize
the biochemical processes responsible for nerve agent activity and inhibition, thereby allowing predictions on compounds unrelated
to those already studied.
Received: 10 October 2001 / Accepted: 13 November 2002 / Published online: 1 April 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: M. M. Hurley e-mail: hurley@arl.army.mil |
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Keywords: | : Acetylcholinesterase – IMOMM – Nerve agent – Simulation |
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