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.