Several studies have indicated superior performance when focusing on the specific amino acids that make up the binding site, instead of considering entire protein sequences. Therefore, we used Z-scale descriptors to describe the amino acids within the binding pocket individually. These Z-scales account for 26 physicochemical properties of each amino acid, which are then reduced to five principal components using Principal Component Analysis (PCA). The first three components correspond to lipophilicity, volume/polarizability, and polarity. Random-Stratified Split. The data set was split into 80/20 training/test sets and was stratified to account for the distribution of the different SLC6 members, i.e., each protein member contributed 80% of its data to the training set and the remaining 20% to the test set. The splitting was performed without considering other factors such as pIC50 or chemical space distribution, essentially randomly assigning data to training and test sets within each protein member.