Virtual screening,docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis |
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| Authors: | Leonardo da Costa Bastos Felipe Rodrigues de Souza Ana Paula Guimarães Mehdi Sirouspour Teobaldo Ricardo Cuya Guizado Pat Forgione |
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| Affiliation: | 1. Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, RJ 22290-270, Brazil;2. Department of Chemistry, Federal University of Vi?osa, Vi?osa, MG 36570-000 Brazil;3. Department of Chemistry &4. Biochemistry, Concordia University, Montreal, QC, Canada;5. Faculty of Technology, University of the State of Rio de Janeiro, Resende, RJ 27.537-000, Brazil |
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| Abstract: | In the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (DHFR) as a means of a novel drug therapy against plague. Potential inhibitors of DHFR from Yersinia pestis (YpDHFR) were selected by virtual screening and subjected to docking, molecular dynamics (MD) simulations, and Poisson–Boltzmann surface area method, in order to evaluate their interactions in the active sites of YpDHFR and human DHFR (HssDHFR). The results suggested selectivity for three compounds that were further used to propose the structures of six new potential selective inhibitors for YpDHFR. |
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| Keywords: | plague Yersinia pestis YpDHFR virtual screening docking molecular dynamics selective inhibition |
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