1 a Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ , Brazil.
2 b Department of Chemistry , Federal University of Viçosa , Viçosa , MG , Brazil.
3 c Faculty of Technology , University of the State of Rio de Janeiro , Resende , RJ , Brazil.
4 d Department of Chemistry , Federal University of Lavras , Lavras , MG , Brazil.
5 e Federal Institute of Education , Science and Technology , Vila Velha , ES , Brazil.
6 f Department of Chemistry and Biochemistry , Concordia University , Montreal , Canada.
7 g Faculty of Management and Informatics , University Hradec Kralove , Hradec Kralove , Czech Republic.

Analysis of Coxiela burnetti dihydrofolate reductase via in silico docking with inhibitors and molecular dynamics simulation.

J Biomol Struct Dyn. 2017 Oct;35(13):2975-2986

Authors: de Souza FR, Guimarães AP, Cuya T, de Freitas MP, Gonçalves ADS, Forgione P, Costa França TC

Abstract

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.

PMID: 27726597 [PubMed - indexed for MEDLINE]