1 a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.
2 b Department of Chemistry , Federal University of Viçosa , Viçosa , MG 36570-000 Brazil.
3 c Department of Chemistry & Biochemistry , Concordia University , Montreal , QC , Canada.
4 d Faculty of Technology , University of the State of Rio de Janeiro , Resende , RJ 27.537-000 , Brazil.
5 e Laboratory of Molecular Modeling, Chemistry Department , Federal University of Lavras , Lavras , MG , Brazil.
6 f Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.

Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.

J Biomol Struct Dyn. 2016 Oct;34(10):2184-98

Authors: Bastos Lda C, de Souza FR, Guimarães AP, Sirouspour M, Cuya Guizado TR, Forgione P, Ramalho TC, França TC

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.

PMID: 26494420 [PubMed - indexed for MEDLINE]