Prior to IFD, the designed compounds were energy optimization using LigPrep in Schrödinger software with OPLS3 force field , resulting in the generation of corresponding 3D conformations. Subsequently, the Epik algorithm was employed for ionization handling at a pH value of 7.0 ± 2.0. The target protein structure was retrieved from PDB database . The grid box on SERT was defined using the co-crystalized ibogaine. During the IFD, 20 poses were generated for each compound. The IFD complexes were evaluated and ranked based on energy using the Prime and Glide XP scoring function . All graphical images are generated using the PyMOL software .