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, Oksana Lockridge, P. Masson

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1592-1607
Number of pages16
JournalRussian Chemical Bulletin
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Supercomputers
Polymorphism
Carboxylesterase
Cholinesterases
Esterases
Enzymes
Metabolism
Pharmaceutical Preparations
Medicine
Catalyst activity
Esters
Proteins

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

  • Chemistry(all)

Cite this

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.; Kulakova, A. M.; Kots, E. D.; Makhaeva, G. F.; Delacour, H.; Lockridge, Oksana; Masson, P.

In: Russian Chemical Bulletin, Vol. 65, No. 6, 01.06.2016, p. 1592-1607.

Research output: Contribution to journalArticle

Varfolomeev, S. D. ; Lushchekina, S. V. ; Nemukhin, A. V. ; Kulakova, A. M. ; Kots, E. D. ; Makhaeva, G. F. ; Delacour, H. ; Lockridge, Oksana ; Masson, P. / 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. In: Russian Chemical Bulletin. 2016 ; Vol. 65, No. 6. pp. 1592-1607.
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AU - Kulakova, A. M.

AU - Kots, E. D.

AU - Makhaeva, G. F.

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