version date: 1 December 2006 Predicted △ binding free energy 3000 4000 Hint Score Fig 3 Prediction of the binding free energy of a new potential bovine typsin ligand, from the protein-ligand HINT score It is more difficult to find a good relationship between experimental and computational data, for a heterogeneous set of protein-ligand complexes, characterized by different active site polarity, igands with diverse chemical nature, and inhibition constants varying among 10 or more orderd of magnitude [13]. In the following analysis, 93 different crystallographic protein-ligand complexes were examined and scored, in order to define a general relationship between AG and Hint score Experimental and calculated data, with both the protein nature and the crystallographic resolution values, are reported in Table 3, while the general relation is shown in Fig. 4 Table 3 PDB code Protein Crystal resolution(A) AG binding (kcal/ mol) Hint score IETT bovine thrombin 2.50 2131 IETR bovine thromb IUVT 1A2C human thrombin 8.97 3019 LOw human human thrombi ICu 1C4V human thrombin 10 human thrombin 2.07 IKTT human thrombin 3586 IOYT humaww Upac. org/publications/cd/medicinal_chemistiy9s10 Fig. 3 Prediction of the binding free energy of a new potential bovine typsin ligand, from the protein–ligand HINT score It is more difficult to find a good relationship between experimental and computational data, for a heterogeneous set of protein–ligand complexes, characterized by different active site polarity, ligands with diverse chemical nature, and inhibition constants varying among 10 or more orderd of magnitude [13]. In the following analysis, 93 different crystallographic protein–ligand complexes were examined and scored, in order to define a general relationship between ∆G° and HINT score. Experimental and calculated data, with both the protein nature and the crystallographic resolution values, are reported in Table 3, while the general relation is shown in Fig. 4. Table 3 PDB code Protein Crystal resolution (Å) ∆G°binding (kcal/mol) Hint score 1ETS bovine thrombin 2.30 –11.17 3623 1ETT bovine thrombin 2.50 –8.00 2131 1ETR bovine thrombin 2.20 –10.49 2848 1UVT bovine thrombin 2.50 –10.38 1834 1A2C human thrombin 2.10 –8.97 3019 1A4W human thrombin 1.80 –8.05 3110 1BHX human thrombin 2.30 –9.30 2283 1D6W human thrombin 2.00 –8.10 4005 1FPC human thrombin 2.30 –9.52 2299 1C4U human thrombin 2.10 –14.09 3882 1C4V human thrombin 2.10 –14.67 4390 1C5N human thrombin 1.50 –6.39 2334 1C50 human thrombin 1.90 –4.75 2498 1D4P human thrombin 2.07 –8.57 3363 1KTT human thrombin 2.10 –8.33 3586 1OYT human thrombin 1.67 –9.85 3660 Hint Score 0 1000 2000 3000 4000 ∆G° (kcal/mol) -2 -4 -6 -8 -10 Predicted binding free energy new ligand <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006