we have performed node-weakening analysis by removing the nodes corresponding to the residues located at the interface between PaHisGS and PaHisZ, where the SPM goes through both proteins (5 nodes on PaHisGS and 7 nodes on PaHisZ), and calculating the change in CPL (characteristic path length) upon removal of each node (Supplementary Table ). We then selected the three residues displaying the highest impact on the CPL and performed molecular dynamic simulations of four selected in-silico mutants of PaATPPRT (Y105A-PaHisGS, Y105F-PaHisGS, N185A-PaHisZ, and K186D-PaHisZ), with the aim of disrupting the communication pathway between PaHisGS and PaHisZ. When comparing the SPM of the WT-PaATPPRT with those of the various mutants we generated in-silico, we see that the pathway is slightly reorganized without displaying critical changes that disrupt the communication signal between the two proteins (Supplementary Fig. ). These results are in line with a proposal that allosteric activation is due to a global "nesting" effect of PaHisZ over PaHisGS, with a preferred but not unique allosteric activation pathway.