## 2 Materials and Methods
### Molecular Docking  
We utilized GOLD v4.1.2 or Genetic Optimization Ligand for Docking software (developed by Cambridge Crystallographic Data Centre, UK) to conduct Md analysis [41]. The procedure involves six sequential steps. The initial step (I) involves eliminating ligands, heteroatoms, and unnecessary water molecules, retaining only those essential for the active site. In this instance, none of the water molecules were implicated in the receptor's active site. The subsequent step (II) entails the addition of hydrogen atoms, including those necessary for defining accurate ionization and tautomeric states. The third step (III) is centered around delineating the active site. Among the various methods provided by GOLD for active site definition, the selection was made to utilize a list of atoms or residues modes. The fourth stage (IV), dedicated to configuring ligand parameters, involves performing energy minimization through the utilization of the Hyperchem v8.0 software [42]. This is necessary because GOLD does not modify bond lengths, angles, or rigid bond rotations [24]. Moving to the fifth step (V), which involves the selection of a fitness function, GOLD provides a range of options. Opting for the Piecewise Linear Potential (PLPchem) fitness function, regarded as the most effective scoring function in GOLD [24], was deemed appropriate. The employed PLPchem score is an empirical fitness function meticulously refined for pose prediction, serving to model the steric complementarity between the protein and the ligand. The final step (VI) involves configuring the settings for the docking solution. This encompasses setting the number of Genetic Algorithms (GA) runs to 100 solutions (results) per inhibitor, factoring in the root mean square deviation (RMSD) and cluster size. The default configurations were adhered to in this regard. To validate the results, a self-docking approach was employed, wherein each target's original ligand naturally occurring in the active site was redocked to its corresponding target. This validation process involved fixing RMSD to zero. By ensuring that the original ligand was accurately positioned within the active site, this method confirmed the reliability and accuracy of the docking results. Our investigation focused on examining the inhibitory potential of five compounds (Table 1) sourced from the PubChem database in sdf format. These compounds were tested against six neuroblastoma (NB) targets [43], namely Ageladine A (Mol1), Oroidine (Mol2), Strepoxazine A (Mol3), Cyclooroidine (Mol4), and Taurodispacamide A (Mol5). The obtained Md results were analyzed using Discovery Studio Visualizer (DSV), v 20.0 [44]. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Code** & **2D Structure** & **Source** \\ \hline Mol1 & & \\ (Ageladine A) & & \\ PubID 1: 10089677 & & \\ MW 2: 357.00 g/mol & & \\ F 3: C\({}_{10}\)H\({}_{7}\)Br\({}_{2}\)N\({}_{5}\) & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: The chemical properties of the studied compounds and their structures. The NB targets were obtained from the Protein Data Bank (PDB) [49], and were prepared following the step I explained above. The targets used for docking, along with their corresponding parameters, are presented in Table 2. \begin{table}
\begin{tabular}{c c c c c c} \hline
**PDB ID** & 2 JIM & 3 DEI & 4 FA6 & 6 USR & 7 LQZ & 4 EKK \\ \hline
**Code** & FAK & Ca3 & PI3K & TERT & TRPV1 & AKT1 \\  & & & Phosphatidylinositol & & & \\
**Target** & \begin{tabular}{c} Focal Adhesion \\ Kinase 1 \\ \end{tabular} & Caspase-3 & \begin{tabular}{c} 4,5-bisphosphate 3-kinase \\ catalytic subunit gamma \\ isoform \\ \end{tabular} & \
\begin{tabular}{c} Telomerase \\ reverse \\ transcriptase \\ \end{tabular} & Osm-9-like TRP &
\begin{tabular}{c} RAC-alpha \\ serine/threonine- \\ protein kinase \\ \end{tabular} \\ \hline \end{tabular}
\end{table} 
Table 2: Target enzymes and their associated codes.