## 4 Discussion
The diversity in the types and number of interactions formed by each ligand supports the idea that their distinct structures influence their binding modes and interaction dynamics with VLP. PGN's larger molecular surface area and higher solvent accessibility further suggest that it occupies more space in the interaction, likely contributing to a more extended conformation during the binding process. The structural rigidity and flexibility of VLP were also assessed through RMSF and SSE. RMSF values confirmed that most residues of VLP remained stable, with minimal fluctuations, suggesting that the protein backbone does not experience significant changes during the complex formation. The distribution of alpha helices and beta strands revealed a similar pattern in both VLP complexes. The VLP-PGN complex had 9.0% of its structure in SSE, predominantly composed of alpha helices. This result highlights the structural rigidity required for ligand binding, allowing only a small proportion of beta strands to be flexible. Similarly, the VLP-\(\beta\)-glucan complex exhibited a slightly lower SSE value of 8.75%. Still, the distribution of alpha helices and beta strands remained comparable, reinforcing the overall structural stability of the protein in both interactions. Further analysis of ligand dynamics revealed that PGN demonstrated more fluctuation in its RMSF than \(\beta\)-glucan, suggesting that PGN may exhibit higher flexibility during the binding process. PGN, with its larger MolSA and higher SASA, likely interacts more extensively with its environment than \(\beta\)-glucan, which is more compact. The differences in these properties could indicate PGN's more extended conformation and more significant potential for multiple interaction sites with VLP. The PCA and DCCM analysis offered further insights into the conformational dynamics of VLP when docked with PGN and \(\beta\)-glucan. Both ligands induced significant conformational changes in the VLP active pocket, with the PCA results revealing that the VLP-PGN complex experienced a variance drop of 80.8% at the first four eigenmodes. In contrast, the VLP-\(\beta\)-glucan complex showed a similar drop at seven eigenmodes. These findings suggest that both ligands effectively modulate the flexibility and stability of VLP, albeit with slight differences in the number of eigenmodes involved in the initial variance drop. The DCCM analysis confirmed that PGN and \(\beta\)-glucan induce distinct but significant alterations in the correlated motions of the VLP structure, with PGN demonstrating a more pronounced effect on VLP's dynamic behavior than \(\beta\)-glucan. These results highlight the critical role of ligand-induced conformational changes in modulating the functional interactions between VLP and its ligands. Last, VLP-PGN demonstrated more substantial binding stability than VLP-\(\beta\)-glucan across all simulation time points, with a \(\Delta\)G\({}_{\text{bind}}\) of \(-\)85.41 kcal/mol at 0 ns and decreasing to \(-\)64.65 kcal/mol at 100 ns. In contrast, VLP-\(\beta\)-glucan started at \(-\)66.09 kcal/mol and decreased to \(-\)43.87 kcal/mol. The \(\Delta\)G\({}_{\text{bind}}\)vdW contributed significantly to the binding energy, with VLP-PGN exhibiting stronger interactions. \(\Delta\)G\({}_{\text{bind}}\)H\({}_{\text{bond}}\) was slightly more prominent in VLP-\(\beta\)-glucan, while \(\Delta\)\(\Delta\)G\({}_{\text{bind}}\)Solv GB imposed a higher penalty for VLP-PGN.