## 3 Results and Discussion
### Molecular Docking
#### 3.3.1 The Focal Adhesion Kinase 1  
Focal Adhesion Kinase 1 or FAK is a non-specific protein-tyrosine kinase located in the cytoplasm. It is part of the focal adhesion family, which consists of significant macromolecular complexes. It can be triggered into activation by integrins, growth factors, cytokines, and hormones which play a critical role in transmitting signals that regulate a wide range of cellular processes such as proliferation, differentiation, and migration [52]. Dysregulation of FAK has the potential to contribute to cancer development [53], particularly in relation to the proliferation of neuroblastoma. Its functioning as a transferase enzyme facilitates the phosphorylation of tyrosine residues in cytoskeletal proteins (Ckp) initiated by the adhesion properties of integrins by utilizing adenosine-5\({}^{\prime}\)-triphosphate (ATP), resulting in the production of adenosine-5\({}^{\prime}\)-diphosphate (ADP) and O-phospho-L-tyrosyl-[Ckp]. Its crystal structure was found complexed with ATP in chain A and ADP in chain B, the docking validation shows that ATP was bound in the active site and formed mostly hydrogen bonds with several residues, including the important of them: Gln432, Lys454, and Cys502, with the support of Arg550, Gly429, Gly431, Ile428, Met499, Val436, Ala452, and Leu553. The ATP purine moiety forms several hydrophobic interactions with Ala452, Cys502, and Leu553. These interactions are crucial for phosphorylation. Mol1 is a pyrrole-imidazole alkaloid comprising an imidazole[4,5-c]pyridin group attached to a dibromo-pyrrole moiety. It demonstrates the lowest PLPChem score compared to other compounds targeting FAK (Table 5), which explains its reduced stability and suggests it may not serve as the perfect model for FAK. Mol1 binds to FAK through a crucial conventional hydrogen bond with Cys502, along with seven other residues involved in eight hydrophobic interaction types, including: Ile428, Met499, Val436, Ala452, and Leu553. Those these interactions, the imidazole[4,5-c]pyridin side of Mol1 plays the most significant role. Mol2, Mol3, and Mol4 exhibited nearly identical PLPChem scores (Table 5). Among them, Mol4 performed the best, securing the second rank among all compounds. Its superiority over Mol2, which ranked third, can be attributed to the presence of a dibromo-pyrrole ring. This highly reactive feature allowed Mol4 to position itself deeply within the ATP binding site, enabling crucial binding interactions with two essential residues, Cys502 and Lys454. These residues typically interact with the pyrrole and phosphorus moieties of ATP, respectively, playing a critical role in the phosphorylation process. Mol4 also engaged in other significant hydrophobic interactions, such as pi-alkyl interactions with Ile428, Val436, and Leu553. The cyclisation in Mol4 provided a structural advantage, enhancing its affinity for FAK compared to Mol2. Notably, Mol2's structure underwent a 90\({}^{\circ}\) rotation compared to Mol4, leading it to bind only to Cys502 along with other residues, resulting in a reduced PLPChem score (Table 5). Mol3 ranked fourth among the compounds targeting FAK. It formed important interactions with three key residues involved in phosphorylation, namely: Cys502, Gln432, and \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Ligand** & **PLPChem Score** & **Closest Residues** & **Interactions** & **Length (Å)** & **Fav/Unfav 1** \\  & & Lys276, Lys179, Val164, Met281, Leu156, & Hydrogen Bond & 2.07 & \\ Mol4 & 46.66 & Ala177, & Pi-alkyl & \(>\)3.4 & \\  & & Met227, Asp292, Phe438, & Alkyl & \(>\)3.4 & \\  & & Thr160, Gly159, Ala177, Val164, Met281, & Pi-alkyl & \(>\)3.4 & \\ Mol5 & 51.47 & Met227, Phe438, Thr291, Tyr229, & Alkyl & \(>\)3.4 & \\  & & Glu228, Leu156, & Pi-Sulfur & \(>\)5.0 & \\  & & Arg4, Thr5, Thr6, Ser7 & Halogen (Br) & 3.03 & \\ \hline \hline \end{tabular}  
* \({}^{1}\)Favorable/Unfavorable.  
\end{table} 
Table 5: _Cont._Lys454. Despite this binding, Mol3 achieved a lower PLPchem score compared to Mol2 and Mol4.