Figure 2

Quantifying the residues’ importance. (A) We automatically divided the centrality values into 4 bins to identify the groups highlighted. In the log-betweenness and degree dimensions, the intervals were \((-0.484, 0.886)\) and (1.988, 4.75) for LDLB; (3.613, 4.977) and (1.988, 4.75) for LDHB; (3.613, 4.977) and (10.25, 13.0) for HDHB. (B–C) The HDHB nodes are mainly located at the core of all domains of the FV protein structure, and play a pivotal role in maintaining the structure in place via attractive and repulsive atomic forces. The LDHB nodes are those that despite being connected to only a few nodes, are central to the long-range communication network formed by all residues. Finally, the LDLB residues are located at the surface of FV, with only a few connections and are usually not conserved (Supplementary Tables S2–S3). (D) The closeness centrality is the inverse of the steps necessary to reach every other node in the FV-RIN. Therefore, the most central residues of the protein structure display high closeness values. Using the Pareto front to evaluate the closeness, the degree and the betweenness values of all nodes, we arrive at the most central, well-connected and critical residues of the FV-structure, located at the junction of multiple domains, and most likely holding the structure in its most favorable conformation. Abbreviations: High degree and high betweenness (HDHB); low degree and high betweenness (LDHB); low degree and low betweenness (LDLB); Solvent accessible surface area (SASA). Statistics: One-way ANOVA followed by Tukey’s Post Hoc test. *** p value < 0.001.