## 3 Results and Discussion
### Molecular Docking
#### 3.3.4 Telomerase Reverse Transcriptase  
Telomerase reverse transcriptase, referred to as TERT, is a catalytic subunit of the telomerase enzyme. It is derived from _Tribolium castaneum_ and belongs to the family of ribonucleoprotein polymerases. TERT's primary function is to maintain the ends of telomeres by adding the telomere repeat TTAGGG [66]. Telomerase is responsible for lengthening the telomere sequences at the ends of chromosomes, which helps protect the genomic DNA. It plays a crucial role in determining the maximum number of times a cell can divide and thus plays a significant part in the immortality of cell lines, including cancer cells. TERT, functioning as a transferase enzyme, has a vital role in enabling the phosphorylation of 2\({}^{\prime}\)-deoxyribonucleoside 5\({}^{\prime}\)-triphosphate using DNA (n). This enzymatic activity results in the formation of diphosphate and DNA (n + 1). The crystal structure of TERT comprises a single chain referred to as A, which has been observed to form complexes with the G2P ligand or (phosphor-methyl-phosphonic acid guanylate ester). The docking validation reveals that G2P predominantly engages in hydrogen bonds with several key residues, such as Ala195, Asp301, Gly309, Gln308, Asp254, and Arg194. These interactions are primarily facilitated by the G2P phosphorus tail moiety and are deemed essential for the inhibition mechanism. Mol1 demonstrates a lower PLPChem score when compared to other compounds targeting TERT, which helps explain its reduced stability. This observation raises doubts about Mol1 being an ideal model. Specifically, Mol1 only forms a single interaction with Gln308 involved in phosphorylation and binds at a considerable distance. Additionally, its dibromo-pyrrole ring is attracted to Tyr256, leading to a Pi-Pi Stacked interaction that adversely affects its overall binding with G2P. This steric motion forces Mol1 to interact with other residues, resulting in most of the saved interactions or bonds. Consequently, Mol1's optimal conformation appears to compromise its stability and may interfere with phosphorylation processes. Mol2 outperformed Mol4 in terms of their PLPChem scores (Table 5), making Mol2 the third-ranked compound among all tested compounds. Both Mol2 and Mol4 closely interacted with important residues such as Asp254 and Ala195, while Mol4 also had remarkable interactions with Arg194 and Ala195. Both compounds formed Pi-Pi Stacked and Pi-Alkyl interactions with Tyr256, respectively. In contrast to Mol1, the Pi-Pi Stacked interaction did not negatively impact Mol2's overall stability. This was because Mol2's tail was flexible enough to adjust near Ala255 and Asp254, providing it with a significant advantage over Mol4. Mol2's stabilization primarily relied on hydrophobic interactions, particularly with the dibromo-pyrrole ring and Tyr256, along with crucial carbon-hydrogen bonds with Asp254 that facilitated multiple conventional hydrogen bonds. On the other hand, Mol4's binding to Tyr256 through a Pi-Alkyl interaction caused a 90\({}^{\circ}\) torsion, leading it to adopt a pose close to Arg194 as its best conformation. This slightly affected its PLPChem score, positioning it in the fourth rank due to having the lowest number of interactions, only seven in total. Nevertheless, Mol4's positioning of its imidazole ring near Arg194 and Ala195 still makes it a potential inhibitor candidate for TERT. Mol5 and Mol3 secured the top two rankings among the compounds targeting TERT (Figure 4), as indicated in the PLPChem scores table. They employed distinct inhibition mechanisms. Notably, Mol5 interacted with a key residue same as G2P, which served as the reference inhibitor. It successfully blocked the binding site with 15 interactions, surpassing all other compounds in interaction efficiency with TERT. Mol5 shared a similar mechanism with Mol2, involving a Pi-Pi Stacked interaction with Tyr256 and its dibromo-pyrrole ring. This suggested the importance of this interaction in defining the behavior of all compounds with TERT.