## 2 Results and Discussion
### Molecular Docking Simulation
#### 2.5.1 Insights into FEYNF-NH\({}_{2}\) Self-Assembling Mechanism  
The computer-aided molecular docking simulation was performed herein in order to gain comprehensive insights into the peculiar mechanism governing the self-assembly of the amidated FEYNF peptide. Assuming the chemical structure (2D) of the pentapeptide given in Figure 1a, its spatial conformer (3D) was built directly in the YASARA-Structure program using the \"BuildMol\" command. Subsequently, the initial generated 3D geometry of FEYNF-NH\({}_{2}\) underwent optimization using the molecular mechanics method at the YASARA force field level [56]. The optimized 3D arrangement of the atoms in the FEYNF-NH\({}_{2}\) structure (following energy minimization) is illustrated in Figure 7a. One may observe that the hydrophilic and hydrophobic peptide side chains are found on opposite sides of the peptide backbone. The optimized conformation from Figure 7a was then utilized in molecular docking simulations, serving dual roles as both a flexible ligand and a rigid receptor, to spot the self-assembling mechanism by assessing the peptide-peptide interactions during the dimer formation (Figure 7b). Molecular docking simulations were carried out by assessing 100 docked complexes (poses) of the dimer (FEYNF@FEYNF), using the VINA algorithm. The numerical data obtained for all 100 poses (plotted in Figure 7c) elucidate the correlation between binding energy (\(E_{b}\)) and dissociation constant (\(K_{d}\)) for each docked model. As shown in Figure 7c, an increased value of the dissociation constant for a given docked model corresponds to a higher associated binding energy. Nevertheless, the relationship (\(K_{d}\) vs. \(E_{b}\)) is non-linear and characterized by a monotonically increasing trend. After clustering the 100 peptide dimer conformations, 11 distinct and representative docked models (clusters) were identified. The clusters differ from each other in terms of root-mean-square deviation (RMSD) of atomic positions of at least 5.0 A. Subsequently, Table S2 (in Supplementary Materials) provides detailed information on binding energy (\(E_{b}\)), dissociation constant (\(K_{d}\)) values, and the amino acid residues involved in the peptide-peptide interaction for each cluster. The relation between the binding energy (\(E_{b}\)) and dissociation constant (\(K_{d}\)) after the clustering analysis is represented in Figure 7d. Generally, the lower the values for \(E_{b}\) and \(K_{d}\), the better the affinity, and the peptide-peptide interaction is more favorable, indicating a higher docking score. Consequently, according to Figure 7d and Table S2 (Supplementary Materials) data, the optimum pose for the peptide dimer complex was associated with the lowest binding energy (\(E_{b}=-5.38\) kcal/mol) and dissociation constant (\(K_{d}=113.87\)\(\upmu\)M). The calculated values indicate a strong and stable noncovalent binding interaction between the peptide molecules. This can be attributed to the fact that each distinctive amino acid residue from the FEYNS-NH2 structure (PHE1 (F), GLU2 (E), TYR3 (Y), ASN4 (N), and PHE5 (F)) is involved in the peptide-peptide interaction, as indicated by the data in Table S2. Hence, the best docked FEYNF@FEYNF dimer complex conformation and the corresponding binding interactions are highlighted in Figure 7b. One may see that the peptide structures are oriented in the same direction (parallel), and the intermolecular interactions between the peptide molecules are based on hydrophobic interactions, \(\pi\)-\(\pi\) stacking, and H-bonds (detailed in Table S3, Supplementary Materials). The presence of multiple interacting sites is ideal for the formation of supramolecular gels.