Docking and molecular dynamics studies at trypanothione reductase and glutathione reductase active sites.
A theoretical docking study on the active sites of trypanothione reductase (TR) and glutathione reductase (GR) with the corresponding natural substrates, trypanothione disulfide (T[S]2) and glutathione disulfide (GSSG), is reported. Molecular dynamics simulations were carried out in order to check the robustness of the docking results. The energetic results are in agreement with previous experimental findings and show the crossed complexes have lower stabilization energies than the natural ones. To test DOCK3.5, four nitro furanic compounds, previously designed as potentially active anti-chagasic molecules, were docked at the GR and TR active sites with the DOCK3.5 procedure. A good correlation was found between differential inhibitory activity and relative interaction energy (affinity). The results provide a validation test for the use of DOCK3.5 in connection with the design of anti-chagasic drugs.
Lab. de Modelado Biomolecular, Depto de Quimico-Física y Matemáticas, Facultad de Química, Universidad de la República, Gral. Flores 2124, C.C. 1157, Montevideo, Uruguay.
Federico
F
Iribarne
Margot
M
Paulino
Sara
S
Aguilera
Miguel
M
Murphy
Orlando
O
Tapia
D001665:Binding Sites; D003198:Computer Simulation; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019803:Glutathione Disulfide / Q000737:chemistry / Q000378:metabolism; D005980:Glutathione Reductase / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity
D008024:Ligands; D046911:Macromolecular Substances; D012997:Solvents; C044809:trypanothione; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase; D005978:Glutathione; D013095:Spermidine; D019803:Glutathione Disulfide