title: Molecular modeling studies of Yersinia pestis dihydrofolate reductase.
abstract: Considering the risk represented by plague today as a potential biological warfare agent, we propose cytosolic Yersinia pestis dihydrofolate reductase (YpDHFR) as a new target to the design of selective plague chemotherapy. This enzyme has a low homology with the human enzyme and its crystallographic structure has been recently deposited in the Protein Data Bank (PDB). Comparisons of the docking energies and molecular dynamic behaviors of five known DHFR inhibitors inside a 3D model of YpDHFR (adapted from the crystallographic structure) and human DHFR (HssDHFR), revealed new potential interactions and suggested insights into the design of more potent HssDHFR inhibitors as well as selective inhibitors for YpDHFR.
authors.affiliation: Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, 22290-270, Rio de Janeiro, RJ, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: Oliveira
authors.forename: Magdalena N
authors.initials: MN
authors.lastname: Rennó
authors.forename: César A
authors.initials: CA
authors.lastname: de Matos
authors.forename: Morena D
authors.initials: MD
authors.lastname: Bertuzzi
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Tanos C C
authors.initials: TC
authors.lastname: França
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D015195:Drug Design; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D015203:Reproducibility of Results; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D015010:Yersinia pestis / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D005493:Folic Acid Antagonists; D008024:Ligands; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase