Email this article 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
- Authors: Varfolomeev S.D.1,2, Lushchekina S.V.1, Nemukhin A.V.1,2, Kulakova A.M.2, Kots E.D.1,2, Makhaeva G.F.3, Delacour H.4, Lockridge O.5, Masson P.6
-
Affiliations:
- N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences
- Department of Chemistry, M. V. Lomonosov Moscow State University
- Institute of Physiologically Active Compounds, Russian Academy of Sciences
- Department of Biology, Bégin Military Teaching Hospital
- University of Nebraska Medical Center, Eppley Institute
- Kazan (Volga region) Federal University
- Issue: Vol 65, No 6 (2016)
- Pages: 1592-1607
- Section: Full Articles
- URL: https://journals.rcsi.science/1066-5285/article/view/238443
- DOI: https://doi.org/10.1007/s11172-016-1487-8
- ID: 238443
Cite item
Open Access
Access granted
Subscription Access
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.
About the authors
S. D. Varfolomeev
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Author for correspondence.
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
S. V. Lushchekina
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 4 ul. Kosygina, Moscow, 119334
A. V. Nemukhin
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
A. M. Kulakova
Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Russian Federation, Build. 3,1 Leninskie Gory, Moscow, 119991
E. D. Kots
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences; Department of Chemistry, M. V. Lomonosov Moscow State University
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 4 ul. Kosygina, Moscow, 119334; Build. 3,1 Leninskie Gory, Moscow, 119991
G. F. Makhaeva
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
H. Delacour
Department of Biology, Bégin Military Teaching Hospital
Email: sdvarf@sky.chph.ras.ru
France, 69 Paris Av. 94 163, Saint Mandé
O. Lockridge
University of Nebraska Medical Center, Eppley Institute
Email: sdvarf@sky.chph.ras.ru
United States, Omaha, NE, 68198-5950
P. Masson
Kazan (Volga region) Federal University
Email: sdvarf@sky.chph.ras.ru
Russian Federation, 18 ul. Kremlevskaya, Kazan, 420008
