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Molecular polymorphism of human enzymes as the basis of individual sensitivity to drugs. Supercomputer-assisted modeling as a tool for analysis of structural changes and enzymatic activity of proteins

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Abstract

The nature of individual sensitivity to drugs associated with molecular polymorphism of human enzymes is discussed. The influence of molecular polymorphism on the activity of key human esterases, in particular, cholinesterases and carboxylesterase, responsible for hydrolytic metabolism of ester-containing drugs, is analyzed. A method was developed, which involves supercomputer-assisted modeling as a tool for assessment of molecular mechanism of the impact of point mutations on the catalytic activity of enzymes. This work is a part of a study aimed at elaboration of the concept and methods of personalized medicine.

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

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

    S. D. Varfolomeev, A. V. Nemukhin, A. M. Kulakova & E. D. Kots

  3. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severnyi proezd, 142432, Chernogolovka, Moscow Region, Russian Federation

    G. F. Makhaeva

  4. Department of Biology, Bégin Military Teaching Hospital, 69 Paris Av. 94 163, Saint Mandé, France

    H. Delacour

  5. University of Nebraska Medical Center, Eppley Institute, NE, 68198-5950, Omaha, USA

    O. Lockridge

  6. Kazan (Volga region) Federal University, 18 ul. Kremlevskaya, 420008, Kazan, Russian Federation

    P. Masson

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  1. S. D. Varfolomeev
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Correspondence to S. D. Varfolomeev.

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Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1592—1607, June, 2016.

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Varfolomeev, S.D., Lushchekina, S.V., Nemukhin, A.V. et al. Molecular polymorphism of human enzymes as the basis of individual sensitivity to drugs. Supercomputer-assisted modeling as a tool for analysis of structural changes and enzymatic activity of proteins. Russ Chem Bull 65, 1592–1607 (2016). https://doi.org/10.1007/s11172-016-1487-8

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