Figure 6: The binding mode shared by approved sNRIs with hNET.

The identified salt bridges, hydrogen bonds and hydrophobic interactions were depicted in red, green and blue dashed lines, respectively. The red color (R₁) indicated the chemical moiety with salt bridge and hydrogen bond interaction with residues in the vicinity, while the light blue (R₂) and dark blue (R₃) represented the chemical moiety with only hydrophobic interaction with its nearby residues. Each chemical moiety was generalized by the superimposition of 4 sNRIs in the S1 pocket. The residues in dark (Phe72, Asp75, Val148, Tyr152, Phe317, and Phe323) belonged to the subgroup A₁ (Fig. 5), and the residues in gray (Ala145, Gly149, Ser419, Ser420 and Gly423) were clustered into subgroup A₂ (Fig. 5).