Figure 7. Critical network nodes reveal regulatory sites and pathways.

(a) A series of highly ranked memory nodes in inactive p38γ reveal multiple pathways that extend greater than 20 Å from the docking site to the activation loop. Large circles represent residues with a direct connection to the memory node of interest and small circles represent connected memory nodes. Semi-circles depict residues with an indirect connection to the memory node. The relative amount of flow between residues is indicated by the thickness of solid arrows. Dashed arrows indicate the common residue belonging to the next memory node in the path. Colors correspond to regulatory elements, as labeled. Memory nodes (left to right) include M109-M112, L89-L78, and L77-L174. (b) A significant memory node in the αC-helix of apo p38γ suggests a route for auto-activation by Y326 phosphorylation. (c) A highly ranked memory node in the MAPK insert of activated p38γ reveals a communication pathway to catalytic residues.