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

S. D. Varfolomeev; S. V. Lushchekina; A. V. Nemukhin; A. M. Kulakova; E. D. Kots; G. F. Makhaeva; H. Delacour; O. Lockridge; P. Masson

doi:10.1007/s11172-016-1487-8

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

S. D. Varfolomeev, S. V. Lushchekina, A. V. Nemukhin, A. M. Kulakova, E. D. Kots, G. F. Makhaeva, H. Delacour, O. Lockridge, P. Masson

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1592-1607
Number of pages	16
Journal	Russian Chemical Bulletin
Volume	65
Issue number	6
DOIs	https://doi.org/10.1007/s11172-016-1487-8
State	Published - Jun 1 2016

Keywords

acetylcholinesterase
butyrylcholinesterase
carboxylesterase
high performance computing
individual sensitivity to drugs
molecular dynamics
molecular modeling
molecular polymorphism of enzymes
personalized medicine

ASJC Scopus subject areas

General Chemistry

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10.1007/s11172-016-1487-8

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Varfolomeev, S. D., Lushchekina, S. V., Nemukhin, A. V., Kulakova, A. M., Kots, E. D., Makhaeva, G. F., Delacour, H., Lockridge, O., & Masson, P. (2016). 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. Russian Chemical Bulletin, 65(6), 1592-1607. https://doi.org/10.1007/s11172-016-1487-8

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. / Varfolomeev, S. D.; Lushchekina, S. V.; Nemukhin, A. V. et al.
In: Russian Chemical Bulletin, Vol. 65, No. 6, 01.06.2016, p. 1592-1607.

Research output: Contribution to journal › Article › peer-review

Varfolomeev, SD, Lushchekina, SV, Nemukhin, AV, Kulakova, AM, Kots, ED, Makhaeva, GF, Delacour, H, Lockridge, O & Masson, P 2016, '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', Russian Chemical Bulletin, vol. 65, no. 6, pp. 1592-1607. https://doi.org/10.1007/s11172-016-1487-8

Varfolomeev SD, Lushchekina SV, Nemukhin AV, Kulakova AM, Kots ED, Makhaeva GF 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. Russian Chemical Bulletin. 2016 Jun 1;65(6):1592-1607. doi: 10.1007/s11172-016-1487-8

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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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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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