## 3 Results and Discussion
### External Representative ABFPs on the Representative Antibioticfilm HSPN
The HSPN that plots nodes coordinates from their two most relevant principal components, estimated from a non-redundant set of AF descriptors, is the most real approach to display the peptide's location in the network, allowing a more accurate visual inspection of the similarity and distribution of the 14 representative ABFPs on the reported chemical space (Figure 9A). Figure 9A shows the node and names corresponding to 14 ABFPs in black color, while the other 66 from StarPepDB were labeled according to the colors assigned to each one of the five network communities. As can be observed in Figure 9A, all 14 ABFPs were framed within the antibiofilm HSPN. In fact, the Indolicidin, Protegrin-1 and HBD-3 overlapped perfectly with starPep_00002, starPep_00020 and starPep_00116, respectively. The 14 mechanisms of action classes were distributed among all the five HSPN communities, which may indicate a connection between structural patterns (motifs) found within network communities with the antibiofilm mode of action. In order to illustrate this fact, six ABFPs that showed antibiofilm activity against both bacteria and fungi (pleurocidin, Pac-525, protegrin-1, TetraF2W-RR, WLBU2, and melittin) overlapped perfectly or almost perfectly over different communities. Pleurocidin, Pac-525, protegrin-1 and melittin are evidently overlapped on the communities colored in blue, green, pink and light purple. WLBU2 was also placed in the green community as the Pac-525, probably because both act using similar mechanisms of action involving the interaction with the lipopolysaccharidesaccharides to destroy or penetrate the bacterial membrane. Although TetraF2W-RR is within the antibiofilm space represented by the HSPN, it did not overlap on any specific community. However, it was placed between green and pink communities containing members such as Pac-525, WLBU2, Indolicidin and protegrin-1, whose mode of action is closely related to that reported for TetraF2W-RR (bacterial membrane disruption). These four ABFPs are arginine \(\copyright\)-rich peptides containing repeated units of R, allowing interaction with negatively-charged bacterial membranes, the formation of transmembrane pores, and cell penetration [70]. Figure 9: Visual mining of the 14 ABFPs corresponding to 14 classes of mode of actions on the chemical space of ABFPs. (**A**) Overlapping the 14 representative ABFPs on the set integrated by 66 ABFPs using HSPN. Peptide communities are represented by different colors, while the 14 ABFPs nodes/labels are highlighted in black color. (**B**) Mapping of the representative ABFPs with similarities higher than 0.60 within the antibiofilm HSPN using the Fruchterman–Reingold layout. Figure 9B complements the information extracted from Figure 8A. It shows those representative ABFPs sharing AF similarities > 0.60 with some of the 66 ABFPs extracted from StarPepDB. Black nodes represent the 9 out of the 14 representative ABFPs that fulfill this condition, while the black edges display the similarity relationships between black nodes (origin) and colored nodes (target). Target nodes labeled as starPep_XXXXX retained the same color identifying them at the network communities in Figure 9A. Figure 9B confirms that Indolicidin, Protegrin-1 and HBD-3 share the max. similarity (1.0) with those ABFPs that overlapped with starPep_00002, starPep_00020 and starPep_00116 in Figure 9A. The location of pleurocidin and protegrin-1 was also supported by their highest similarities (0.65 and 1.0), with members of the communities blue (starPep_00496) and pink (starPep_00020), respectively. However, as the pleurocidin shows multiple actions such as membrane disturbance and permeabilization, binding to bacterial DNA and interference with several cellular functions, it also displays similarities with members (starPep_00193, starPep_00051) from two other communities (Figure 9B).