Computational Modeling of the SARS-CoV-2 Main Protease Inhibition by the Covalent Binding of Prospective Drug Molecules

Тип документаJournal Article
Дата публикации2021-04-07
Название журналаSupercomputing Frontiers and Innovations
ИздательSouth Ural State University
КвартильQ3
ISSN24096008, 23138734
  • Computer Science Applications
  • Hardware and Architecture
  • Computational Theory and Mathematics
  • Information Systems
  • Computer Networks and Communications
  • Software
Краткое описание
We illustrate modern modeling tools applied in the computational design of drugs acting as covalent inhibitors of enzymes. We take the Main protease (M pro ) from the SARS-CoV-2 virus as an important present-day representative. In this work, we construct a compound capable to block M pro , which is composed of fragments of antimalarial drugs and covalent inhibitors of cysteine proteases. To characterize the mechanism of its interaction with the enzyme, the algorithms based on force fields, including molecular mechanics (MM), molecular dynamics (MD) and molecular docking, as well as quantum-based approaches, including quantum chemistry and quantum mechanics/molecular mechanics (QM/MM) methods, should be applied. The use of supercomputers is indispensably important at least in the latter approach. Its application to enzymes assumes that energies and forces in the active sites are computed using methods of quantum chemistry, whereas the rest of protein matrix is described using conventional force fields. For the proposed compound, containing the benzoisothiazolone fragment and the substitute at the uracil ring, we show that it can form a stable covalently bound adduct with the target enzyme, and thus can be recommended for experimental trials.
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ГОСТ |
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1. Computational Modeling of the SARS-CoV-2 Main Protease Inhibition by the Covalent Binding of Prospective Drug Molecules // Supercomputing Frontiers and Innovations. 2020. Т. 7. № 3.
RIS |
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TY - JOUR

DO - 10.14529/jsfi200303

UR - http://dx.doi.org/10.14529/jsfi200303

TI - Computational Modeling of the SARS-CoV-2 Main Protease Inhibition by the Covalent Binding of Prospective Drug Molecules

T2 - Supercomputing Frontiers and Innovations

PY - 2020

DA - 2020/09

PB - FSAEIHE South Ural State University (National Research University)

IS - 3

VL - 7

SN - 2313-8734

ER -

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@article{2020,

doi = {10.14529/jsfi200303},

url = {https://doi.org/10.14529%2Fjsfi200303},

year = 2020,

month = {sep},

publisher = {{FSAEIHE} South Ural State University (National Research University)},

volume = {7},

number = {3},

title = {Computational Modeling of the {SARS}-{CoV}-2 Main Protease Inhibition by the Covalent Binding of Prospective Drug Molecules}

}

MLA
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“Computational Modeling of the SARS-CoV-2 Main Protease Inhibition by the Covalent Binding of Prospective Drug Molecules.” Supercomputing Frontiers and Innovations 7.3 (2020): n. pag. Crossref. Web.