Using the same dataset as described above for PTP1B, we used our program to generate per residue correlation and contact matrices as inputs for a Weighted Implementation of Suboptimal Paths (WISP) calculation, as implemented in the Bio3D 81 package. The per residue correlation matrix is generated by identifying the largest linear correlation (in absolute values) between a pair of residues found in any interaction (if one exists), and this is used to create and weight the edges (connections) between the nodes (the residues). The contact matrix is a binary and symmetrical (along the diagonal) matrix that defines if a given residue pair is in contact or not, with residues that have a minimum heavy atom distance ≤ 6 Å in their crystal structures, considered in contact. The contact matrix is used to filter the edges so that only those residues considered in contact are included, see the Methodology section for further details.