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Quantum mechanical/molecular mechanical analysis of mechanisms of enzyme action. Human acetylcholinesterase

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Abstract

The influence of the system separation into the QM and MM parts on the result of quantum mechanical/molecular mechanical (QM/MM) modeling of acetylcholine hydrolysis in the acetylcholinesterase active site was considered. The minimum acceptable quantum subsystem that provides an adequate description of the enzymatic reaction energy profile was identified. The computed energy profiles were analyzed and possible inaccuracies in QM/MM calculations were estimated. The fairly high tetrahedral intermediate stability was demonstrated, which is in a good agreement with the newest experimental observations.

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Authors and Affiliations

  1. N. M. Emanuel’ Institute of Biochemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119334, Moscow, Russian Federation

    S. V. Lushchekina, A. V. Nemukhin & S. D. Varfolomeev

  2. Department of Chemistry, M. V. Lomonosov Moscow State University, 1/3 Leninskie Gory, Moscow, 119991, Russian Federation

    I. A. Kaliman, B. L. Grigorenko, A. V. Nemukhin & S. D. Varfolomeev

Authors
  1. S. V. Lushchekina
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  2. I. A. Kaliman
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  3. B. L. Grigorenko
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  4. A. V. Nemukhin
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  5. S. D. Varfolomeev
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Correspondence to S. V. Lushchekina.

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Dedicated to Academician of the Russian Academy of Sciences O. M. Nefedov on the occasion of his 80th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2154–2162, November, 2011.

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Lushchekina, S.V., Kaliman, I.A., Grigorenko, B.L. et al. Quantum mechanical/molecular mechanical analysis of mechanisms of enzyme action. Human acetylcholinesterase. Russ Chem Bull 60, 2196–2204 (2011). https://doi.org/10.1007/s11172-011-0338-x

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  • DOI: https://doi.org/10.1007/s11172-011-0338-x

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