Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.
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.
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.
Leonardo da Costa
Lda C
Bastos
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.
Felipe Rodrigues
FR
de Souza
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.|b Department of Chemistry , Federal University of Viçosa , Viçosa , MG 36570-000 Brazil.
Ana Paula
AP
Guimarães
c Department of Chemistry & Biochemistry , Concordia University , Montreal , QC , Canada.
Mehdi
M
Sirouspour
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.|d Faculty of Technology , University of the State of Rio de Janeiro , Resende , RJ 27.537-000 , Brazil.
Teobaldo Ricardo
TR
Cuya Guizado
c Department of Chemistry & Biochemistry , Concordia University , Montreal , QC , Canada.
Pat
P
Forgione
e Laboratory of Molecular Modeling, Chemistry Department , Federal University of Lavras , Lavras , MG , Brazil.|f Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.
Teodorico Castro
TC
Ramalho
a Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD) , Military Institute of Engineering , Rio de Janeiro , RJ 22290-270 , Brazil.|c Department of Chemistry & Biochemistry , Concordia University , Montreal , QC , Canada.|f Faculty of Informatics and Management, Center for Basic and Applied Research , University of Hradec Kralove , Hradec Kralove , Czech Republic.
Tanos Celmar Costa
TC
França
D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D005493:Folic Acid Antagonists / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D015010:Yersinia pestis / Q000201:enzymology*
D005493:Folic Acid Antagonists; D008024:Ligands; D013762:Tetrahydrofolate Dehydrogenase
Yersinia pestis; YpDHFR; docking; molecular dynamics; plague; selective inhibition; virtual screening