## 3 Results and Discussion
### Molecular Docking
#### 3.3.5 Osm-9-like TRP Channel 1  
TRPV1, which stands for Osm-9-like Transient Receptor Potential Vanilloid channel 1, is a type of transmembrane protein that functions as a heat sensor. It consists of two parts: the cap domain (gate entrance), which is located in the outer part of the membrane, and the C-terminus domain, which is located in the inner part of the membrane (gate tip), between which the individual chains are located. It enables sensory nerve endings to detect high temperatures through ion channels belonging to the TRP family. The TRP superfamily consists of 28 cation-permeable channels, categorized into six subfamilies based on their sequence similarities: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPA (Ankyrin), TRPML (Mucolipin), and TRPP (Polycystic) [67]. TRPV1 specifically responds to stimuli such as capsaicin, protons, toxins, and temperatures within the noxious range (>42 \({}^{\circ}\)C). This channel serves as a polymodal molecular sensor involved in numerous physiological processes and has been implicated in various human diseases [68].  
TRPV1, belonging to the category of cationic channels, functions as a signal transducer by modulating the membrane potential or intracellular calcium (Ca\({}^{2+}\)) concentration. It achieves this by allowing the passage of Ca\({}^{2+}\) through a pore formed by specific segments within the membrane. These segments, namely transmembrane segments 5 and 6 (S5 and S6), form a flexible selectivity filter due to the absence of hydrogen bonding within and between their pore helices. Additionally, the pore-forming P loop, consisting of segments (S1-S4), remains relatively stable regardless of the channel's state be it closed, partially open, or fully open. The movement of Ca\({}^{2+}\) is regulated by a dual gating mechanism that involves upper gate and lower gate regions.  
The crystal structure of TRPV1 consists of four chains and has been observed to form acomplex with the Resiniferatoxin (RTX) ligand. The docking validation shows that RTX binds to the vanilloid site (VS) coordinated by residues including Arg559, Leu555, Phe593, Ile575, Ile571, Asn553, Tyr513, Leu517, Ala548, and Met549 based on hydrophobic interactions and carbon-hydrogen bonds. These interactions are crucial for the channel inhibition mechanism.  
Mol1 exhibits a lower PLPchem score when compared to other compounds that target TRPV1. However, this disparity in scores does not affect its efficacy. Notably, Mol1 establishes significant interactions with specific residues, such as Leu517, Leu555, Ile517, and Met549, which are crucial for channel opening. Particularly, its dibromo-pyrrole ring forms an attraction with Leu671 through a carbon-hydrogen bond, which is a residue located in S6. These interactions at the VS position Mol1 as a promising candidate for TRPV1 inhibition.  
Mol2, Mol3, Mol4, and Mol5 achieved top rankings based on their PLPchem scores, as shown in Table 5, with a score ranging from 43 to 49, Mol3 ranked first, however, Mol5 emerged as the best candidate, securing the second rank and boasting the highest number of interactions, surpassing all other compounds. All the compounds primarily relied on hydrophobic interactions, particularly Pi-Alkyl, to stabilize in the VS. Notably, Mol2, Mol3, and Mol4 exhibited similar results, each establishing seven interactions with specific residues like Met549 and Leu517, along with other key residues located close to the VS, suggesting the possibility of distinct inhibition mechanisms for each. Remarkably, Mol5 adopted a unique docking orientation (Figure 5), positioning itself vertically with respect to the cap domain and aligning with the S3-S4 and S5-S6 segments. Its dibromo-pyrrole ring formed linkages with residues from both S5 and S6, while its tail connected S3 with S4. In this configuration, Mol5 engaged with twelve different residues, including those critical for the proper functioning of the channel, effectively occupying the entire VS space. As a result, Mol5 emerged as the most promising model for inhibiting TRPV1.