2.7. Docking of α-aminovalerophenone derivatives
All computational procedures were conducted using MOE 2019.01 software (Chemical Computing Group, Montreal, Canada). Structural model of hDAT was obtained by applying homology modeling on hDAT amino acid sequence (Uniprot ID: Q01959) and considering the crystal structure ofDrosophila DAT (dDAT) complexed with methamphetamine as template (Protein Data Bank, 4XP6) (Wang et al., 2015). Although hDAT and dDAT proteins have moderate sequence similarity (56%), the active site is highly conserved (>80%). The obtained hDAT three-dimensional model (RMSD=0.191 Å) was finally prepared by applying the QuickPrep protocol available in MOE. The GBVI/WSA ΔG score function was used for quantifying the free energy of binding of the 100 resulting conformations for each molecule. The drugs were built as (S)-enantiomers in protonated form and they were docked into the hDAT model using the previous protocol.