## 3 Results and Discussion
### Molecular Docking
#### 3.3.6. RAC-Alpha Serine/Threonine-Protein Kinase  
AKT1, also known as RAC-alpha serine/threonine-protein kinase or \"AKR mouse strain Thymoma\", is one isoform of the human AKT protein, alongside AKT2 and AKT3. All three isoforms share a similar structure, including a pleckstrin homology (PH) domain at the N-terminal, an inter-domain linker, a kinase domain, and a hydrophobic motif (HM) (from Ser463 to Ser477) at the C-terminal [69]. AKT1 activation requires two steps: translocation and phosphorylation. In its normal state, AKT1 is found to be inactive, adopting the PH-in conformation. However, multiple triggers can activate AKT1, including the presence of phospholipids produced in the PI3K pathway discussed earlier in this study. The PH domain assists in positioning AKT1 at the cell membrane by binding to PI3K products. This positioning facilitates the phosphorylation of AKT1's Thr308 located in the activation loop region by the phosphoinositide-dependent kinase-1 (PDK1). An additional phosphorylation occurring at Ser473, within the HM, collaborates synergistically to achieve full activation of AKT1 [70]. This activation process utilizes ATP, leading to the production of ADP and O-phospho-L-thereonly-AKT1. Once activated, it phosphorylates various proteins involved in promoting growth signals, angiogenesis, tumor development, metabolism, and cell survival. Additionally, AKT1 inhibits apoptotic processes, making it an appealing target for cancer therapy [71]. Figure 5: The 3D structure shows the most favorable TRPV1 complexes after docking, with the inhibitors (Mol3 and Mol5) displayed in stick form and colored using default atom colors. Its crystal structure represents the active form, also known as the PH-out conformation. It consists of two chain complexes, each one bound with an ANP ligand or Phosphoaminophosphate acid-Adenylate ester in the ATP binding site. The docking validation shows that ANP form equal hydrogen bonds and hydrophobic interactions with several residues, including: Ser7, Thr5, Leu156, Val164, Ala177, Lys179, Glu228, Tyr229, Ala230, and Met281. The ANP amino purine moiety forms key hydrophobic interactions with ATP binding site residues like Glu228, Tyr229, and Ala230. These interactions play a vital role in inhibiting ATP usage, resulting in the cessation of ADP production and the subsequent inactivation of AKT1. Mol1 exhibits a lower PLPChem score compared to other compounds that target AKT1, and this finding is consistent across all the targets examined in this study. Despite the lower PLPChem score, Mol1 stands out as an ideal model due to its significant interactions with AKT1, ranking second in terms of the number of interactions formed (17 interactions/bonds). Notably, ten of these interactions involve its dibromo-pyrrole ring. The lower PLPChem score can be explained by the fact that the dibromo-pyrrole ring is rotated by approximately 20\({}^{\circ}\) to adopt the optimal conformation required for forming all these interactions. Specifically, Mol1 forms interactions with crucial residues in the ATP binding site, such as Ala230, Tyr229, and Glu228, with the latter forming a halogen interaction with one of Mol1's bromine atoms. Additionally, it interacts with residues from the PH domain, including Leu156, Val164, Ala177, and Lys179, which are vital for AKT1's active-inactive cycle. Moreover, Mol1 engages in Pi-Sulfur interactions with Met281 and Met227, potentially leading to an irreversible linkage that blocks ATP usage. Mol4 outperformed Mol2, as evident from their PLPChem scores (Table 5). Mol4 stood out with a significantly higher number of interactions, almost double that of Mol2 (12 interactions). Interestingly, none of these interactions occurred near any of the ATP binding site residues. Instead, both Mol4 and Mol2 bound to residues within the PH domain, such as Leu156, Val164, Ala177, and Lys179, primarily through hydrophobic interactions, including alkyl and Pi-alkyl types.