## 3 Results
### Virtual Screening and Docking Experiment  
The selected compounds were evaluated in the model to predict their LogK\({}_{\text{d}}\) value, and the docking experiment was used to determine the binding mode of the ligand to the dopamine transporter pocket. The predicted LogK\({}_{\text{d}}\) values, obtained with the computational model, and the binding affinities achieved in the docking experiment are shown in Table 5. \begin{table}
\begin{tabular}{c c c c c c c c c c c c} \hline
**Target** & **Technique** & **Structures** & **No Var.** & **N (Train)** & **N (Test)** & **R\({}^{2}\)** & **R\({}^{2}\)**\#lllllllll} \(\mathbf{Q}^{2}\)**LMO** & **RMSE\({}_{\text{var}}\)** & **R\({}^{2}\)**\#lllllll} & **Ref.** \\ \hline D\({}_{2}\) & PLS & Congeneric & 5 & 27 & 7 & 0.731 & 0.696 & 0.623 & _nr_ & _nr_ & 0.742 & [27] \\ A\({}_{\text{2A}}\) & ICP-MLR & Congeneric & 5 & 25 & 10 & 0.901 & 0.875 & 0.850 & _nr_ & _nr_ & 0.540 & [28] \\ DAT & PLS & Congeneric & 2 & 26 & 10 & 0.842 & _nr_ & 0.761 & 0.746 & 0.546 & 0.997 & [30] \\ DAT & MLR & Congeneric & 10 & 69 & _np_ & 0.814 & 0.692 & _nr_ & _nr_ & _nr_ & _nr_ & [29] \\ DAT & PLS & Congeneric & 10 & 69 & _np_ & 0.807 & 0.732 & _nr_ & _nr_ & _nr_ & _nr_ & [29] \\ DAT & GFA & Congeneric & 10 & 69 & _np_ & 0.718 & 0.67 & _nr_ & _nr_ & _nr_ & _nr_ & [29] \\ DAT & MLR & Diverse & 4 & 45 & 12 & 0.755 & 0.729 & 0.680 & 0.648 & 0.409 & 0.709 & TW \\ \hline \end{tabular}  
* PLS: partial least squares; _nr_: not reported; ICP-MLR: Intelligent Consensus Predictor Multiple Linear Regression; MLR: Multiple Linear Regression; GFA: Genetic Function Approximation; _np_: not performed; TW: this work.  
\end{table} 
Table 4: Comparison between computational models developed to identify novel compounds with potential radiopharmaceutical applications. Figure 8 shows that the docked structures fit acceptably with the available L-dopamine X-ray crystal structures; all inhibitors were properly oriented at the active center of the dopamine transporter (Figure 8). To validate the docking experiments, we redocked dopamine with its receptor using the same methodology as with the other compounds. The RMSD obtained from the redocking of dopamine (reference ligand) was 0.85 A, which is within the acceptable range (<2.0 A) according to the reviewed literature [42]. This result confirms that the docking parameters we used in this work accurately reproduce the crystallographic pose found in the Protein Data Bank (PDB: 8Y2D) [43]. The best poses were conserved and were those that had a \(\Delta\)G \(\leq-6.0\) kcal/mol, which is the common threshold for strong protein-ligand interactions [77]. Figure 8: Alignment of all docked ligands in complex with the dopamine transporter: (**A**) represents the re-docked result of L-dopamine (in yellow), obtained from Protein Data Bank X-ray crystallography structure (PDB id: SY2D), and the L-dopamine re-docked poses (in magenta). (**B**) represents the best docking poses of other dopamine transporter inhibitors. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Molecules** & **Predicted** & \(\Delta\)**G\({}_{\text{binding}}\)** & **RMSD (Å)** & \(\mathbf{N}^{\circ}\)**H-Bond** \\  & **LogK\({}_{\text{d}}\)** & **(kcal/mol)** & **(Rank)** & \\ \hline Modafinil (001) & **2.386** & \(-\)**6.669** & 2.187 (5) & 0 \\ Phentermine (002) & 3.538 & \(-\)5.278 & 2.449 (2) & 1 \\ Procaine (003) & **2.713** & \(-\)**6.452** & 2.227 (1) & 1 \\ Phenmetrazine (004) & 4.024 & \(-\)5.336 & 3.063 (2) & 0 \\ Diethylpropion (005) & 3.517 & \(-\)5.610 & 2.814 (3) & 1 \\ Benztropine (006) & **2.449** & \(-\)**6.417** & 1.568 (2) & 2 \\ Fencamfamine (007) & 3.405 & \(-\)5.993 & 3.070 (1) & 1 \\ Sibutramine (008) & 4.053 & \(-\)6.012 & 2.795 (2) & 1 \\ Ioflupane (009) & **3.088** & \(-\)**7.303** & 1.127 (1) & 2 \\ Armodafinil (010) & **2.386** & \(-\)**6.436** & 2.838 (2) & 2 \\ Pseudoephedrine (011) & 4.024 & \(-\)5.742 & 2.332 (2) & 1 \\ \hline \hline \end{tabular} In bold are highlighted the best results.  
\end{table}