Analysis of Coxiela burnetti dihydrofolate reductase via in silico docking with inhibitors and molecular dynamics simulation
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
- Klíčová slova
- Coxiella burnetii, Q fever, dihydrofolate reductase, docking, molecular dynamics,
- MeSH
- antagonisté kyseliny listové chemie farmakologie MeSH
- bakteriální proteiny antagonisté a inhibitory MeSH
- Coxiella burnetii účinky léků metabolismus MeSH
- dihydrofolátreduktasa chemie metabolismus MeSH
- katalytická doména MeSH
- lidé MeSH
- ligandy MeSH
- racionální návrh léčiv MeSH
- simulace molekulární dynamiky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonisté kyseliny listové MeSH
- bakteriální proteiny MeSH
- dihydrofolátreduktasa MeSH
- ligandy MeSH
Coxiella burnetii is a gram-negative bacterium able to infect several eukaryotic cells, mainly monocytes and macrophages. It is found widely in nature with ticks, birds, and mammals as major hosts. C. burnetii is also the biological warfare agent that causes Q fever, a disease that has no vaccine or proven chemotherapy available. Considering the current geopolitical context, this fact reinforces the need for discovering new treatments and molecular targets for drug design against C. burnetii. Among the main molecular targets against bacterial diseases reported, the enzyme dihydrofolate reductase (DHFR) has been investigated for several infectious diseases. In the present work, we applied molecular modeling techniques to evaluate the interactions of known DHFR inhibitors in the active sites of human and C. burnetii DHFR (HssDHFR and CbDHFR) in order to investigate their potential as selective inhibitors of CbDHFR. Results showed that most of the ligands studied compete for the binding site of the substrate more effectively than the reference drug trimethoprim. Also the most promising compounds were proposed as leads for the drug design of potential CbDHFR inhibitors.
b Department of Chemistry Federal University of Viçosa Viçosa MG Brazil
c Faculty of Technology University of the State of Rio de Janeiro Resende RJ Brazil
Department of Chemistry Federal University of Lavras Lavras MG Brazil
e Federal Institute of Education Science and Technology Vila Velha ES Brazil
f Department of Chemistry and Biochemistry Concordia University Montreal Canada
g Faculty of Management and Informatics University Hradec Kralove Hradec Kralove Czech Republic
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