Figure 6

The allosteric coupling between the PIF pocket and the activation loop is preserved with modelled ligand nodes. In A the active PDK1 structure is shown as a ribbon diagram with PS48 as a stick structure, the activation loop is picked out with the arrow. The PIF pocket cavity is shown in B and the K-means cluster centres for this cavity are shown in C. The allosteric profile of the PIF pocket nodes is shown in F, with the direct ligand contacts shown as grey bars and the activation loop as a black bar above the graph. There is a clear peak in correlation at the activation loop, as in figure 3. For comparison the allosteric profile for the liagnd interacting residues in the absence of the centroids is shown in grey and here the activation loop is no longer dominant. The inactive PDK1 structure is shown in D, with the four missing residues modelled onto the activation loop, which is picked out with the arrow. The PIF pocket cavity is shown space filled. The K-means clustered nodes are shown in E against the space filled PDK1. The allosteric coupling of the PIF pocket nodes to PDK1 is shown in G and remarkably the activation loop correlation peak is still dominant in the large lobe. In contrast, when the modelled ligand is removed from the network and the allosteric profile for the PIF pocket ligand interacting residues calculated there is no longer a dominant small lobe peak at the activation loop, grey curve in C.