## 4 Discussion
### Analysis of Conformational Parameters and Interaction Profiles  
The high RMSD values (\(>\)50 A) observed for all analyzed molecules across all enzymes indicate substantial spatial variation in the predicted binding poses. This is a typical feature of blind rigid-body docking simulations, where the entire protein surface is sampled rather than being restricted to a predefined active site, and the ligand is treated as a fully rigid structure without accounting for conformational flexibility. In this study, a 2 A RMSD threshold was used solely for clustering geometrically similar poses. However, the high absolute RMSD values reflect the wide conformational space explored by the ligands. In blind rigid-body docking using AutoDock, RMSD is calculated relative to the reference pose--usually the lowest-energy conformation--and not relative to a known crystallographic binding site. Thus, elevated RMSD values in this context do not imply poor accuracy or instability, but instead indicate that ligands sampled diverse and spatially distinct regions of the protein surface. This behavior is expected when the docking grid encompasses the entire protein structure. The torsional free energy provides additional insights into the conformational flexibility of the ligands upon binding. Linalool and AA consistently exhibit higher torsional energies (e.g., +1.49 kcal/mol for linalool and +4.47 kcal/mol for AA across all enzymes), suggesting a greater degree of conformational flexibility and the potential to adopt multiple orientations within the active site. Conversely, terpen like menthol (e.g., +0.60 kcal/mol for COX-1) and limonene (e.g., +0.30 kcal/mol for COX-1) generally display lower torsional energies, pointing to more rigid and stable binding poses. Such stability can contribute to more effective enzymatic inhibition. The most critical aspect of this study lies in the detailed analysis of specific amino acid residue interactions and their overlap with known catalytic sites, as shown in Tables 5 and 6. This \"match\" provides strong evidence for the potential mechanism of inhibition. For COX-1 and COX-2, both enzymes share considerable homology in their active sites, and this is reflected in the terpene interactions. The key active site residues for COX-1 include TYR385, HIS388, and TRP387. For COX-2, TYR385, SER530, and VAL116 are among the critical residues. Our results show that \(\alpha\)-pinene and \(\beta\)-pinene consistently interact with TYR385, HIS388, and TRP387 in both COX-1 and COX-2 (Table 6). Menthol and linalool also show strong interactions with HIS388 and TYR385 in both enzymes. This suggests a potential for direct interference with the catalytic machinery or with substrate access. These findings support the hypothesis that specific terpen may modulate enzyme function by targeting residues essential for catalytic activity, even under the constraints of blind rigid-body docking. 5-LOX is a crucial enzyme for leukotriene biosynthesis, with catalytic residues including HIS367, HIS372, HIS550, TYR181, and TRP599. Our study uniquely identified linalool as the only terpene establishing stable contacts with multiple active site residues of 5-LOX, namely, LEU414, TRP599, ALA603, and TYR181. Despite its overall weaker binding affinity compared to some other terpen (higher Ki), this specific interaction profile with the active site residues suggests a direct mode of action, potentially hinting at a more selective inhibitory mechanism for linalool on 5-LOX than other terpen. The lack of direct matches for other terpen, even with favorable binding energies (e.g., limonene and menthol), suggests that their inhibitory effect might be allosteric or involves residues not explicitly listed as \"catalytic\" in the current literature for 5-LOX active site definition, warranting further investigation. PLA\({}_{2}\) is the enzyme that initiates the arachidonic acid cascade. Its key active site residues include HIS47, CYS44, TYR51, and PHE5.