1. Ensemble Results of PIM1 PIM1-15-6 PIM1-77-5

2. Ensemble Results of GSK3 GSK3-79-2 GSK3-63-18 GSK3-59-2

3. Ensemble Results of EGFR EGFR-0-5 EGFR-70-25 EGFR-49-1 EGFR-89-6 EGFR-0-19

5. GSK3

6. EGFR

7. GSK3-79-2 LEU132 ASP133 LYS85 GLY68 ASN64 GLN185 ASP200 LEU188 ASN186 PIM1-15-6 LEU120 GLU121 LYS67 GLY45 GLU171 ASP186 LEU174 ASN172 EGFR-70-25 THR766GLN767 SER696 ARG81 7 ASP831 LEU768 MET769 ASN818 EGFR-49-1 ASP831 GLN767 GLU734 ASP813 LEU820 ASN818 LYS730 0.27 -2.74 -0.54 -2.91

8. Conformations Predicted Using Single Conformation Docking GLU121 PIM1 GSK3-rank-1 ARG133 GLU97 Binding mode of kinases complexed with Ru-inhibitor, HB12. BLUE is the crystal conformation and Purple is obtained using single conformation molecular docking. Predictions of the location and conformation of the bound ligand in PIM1 matched the crystallographic data very closely as shown in Figure. With GSK3β, HB12 shows multiple binding conformations, see Figure. In the lowest binding energy conformation (rank1), the compound forms a hydrogen bond with residue GLU97. Another conformation is also predicted characterized by a hydrogen bond with residue ASP133 (corresponding residue in PIM1 is GLU121), however, the inhibitor itself is rotated 180° in comparison with the bound conformations. GSK3-rank-2 ARG133

9. GLU121 PIM1 GSK3 ARG133 Blue: Crystal Structures (PIM1 2BZH.pdb, GSK3, Unpublished) Purple: Predicted Structures The two predicted conformations are within 2.0 angstroms compared with the Crystal structure. Conformations showed here are the most productive (lowest energy with entropy correction for PIM1 and GSK3) The Most Productive Conformations from Ensemble Docking

10. Conformation Fluctuation in Cluster

11. Slices after this are backup slices which show the conformations in detail.

12. GSK3-79-2 LEU132 ASP133 LYS85 GLY68 ASN64 GLN185 ASP200 LEU188 ASN186

13. GSK3-63-18 LEU132 ASP133 LYS85 ASN64 ASN186 ASP200 LEU188 TYR134

14. GSK3-59-2 LEU132 ASP133 LYS85 ASN64 ASN186 ASP200 LEU188 TYR134 GLN185

15. EGFR-0-5 THR766 GLN767 SER696 ARG817 ASP831 LEU768 MET769 ASN818

16. EGFR-70-25 THR766GLN767 SER696 ARG817 ASP831 LEU768 MET769 ASN818

17. EGFR-49-1 ASP831 GLN767 GLU734 ASP813 LEU820 ASN818 LYS730

18. EGFR-89-6 THR766 GLN767 ARG817 ASP831 LEU768 MET769 ASN818LEU820

19. EGFR-0-19 THR766 GLN767 ARG817 ASP831 LEU768 MET769 ASN818LEU820

20. PIM1-15-6 LEU120 GLU121 LYS67 GLY45 GLU171 ASP186 LEU174 ASN172

21. PIM1-77-5 LEU120 GLU121 LYS67 GLY45 GLU171 ASP186 LEU174 ASN172