version date: 1 December 2006 Table 1 Compound HINT CLOG-P anthrace 4.45 4.49 1.3-butadiene n-butylamine 0.97 hexachlorobenzene 5.79 642 N-nitrosomorpholine 0.55 0.14 cortisone 0.49 testosterone 3.35 HINT PRACTICAL APPLICATIONS 1. PROTEIN-LIGAND INTERACTIONS Within an homogeneous biological set, HINT can be easily used to score and predict the free energy associated to protein-ligand complex formation. Starting from good crystallographic data and well experimentally determined Ki or ICso values (Table 2), it is possible to obtain linear relationships between experimental AG and computationally calculated HINT score values Table 2 reports the HiNT score protein-ligand values calculated for two different homogenous set, formed, respectively, by eight bovine trypsin-ligand complexes and by nine tryptophan synthase-ligand complexes, for which experimental inhibition constants are reported in literature Table 2 PDB code △G° bindin(kca/mo) Hint score ITNJ ITNI ITNG 3PTB PPH bovine trypsin 804 2663 CX9 2TRS 720 tryptophan synthethase tryptophan synthase 2TSY tryptophan synthethase <www.iupac.org/publications/cd/medicinalchemistry/>8 Table 1 Compound HINT CLOG-P anthracene 4.45 4.49 1,3-butadiene 1.76 1.90 n-butylamine 0.97 0.92 cyclopentane 2.94 2.80 hexachlorobenzene 5.79 6.42 N-nitrosomorpholine –0.41 –0.64 aldosterone 0.55 –0.14 cortisone 0.49 0.20 testosterone 3.35 3.35 HINT PRACTICAL APPLICATIONS 1. PROTEIN–LIGAND INTERACTIONS Within an homogeneous biological set, HINT can be easily used to score and predict the free energy associated to protein-ligand complex formation. Starting from good crystallographic data and well experimentally determined Ki or IC50 values (Table 2), it is possible to obtain linear relationships between experimental ∆G° and computationally calculated HINT score values. Table 2 reports the HINT score protein-ligand values calculated for two different homogenous set, formed, respectively, by eight bovine trypsin-ligand complexes and by nine tryptophan synthase-ligand complexes, for which experimental inhibition constants are reported in literature. Table 2 PDB code protein ∆G°binding (kcal/mol) Hint score 1TNJ bovine trypsin –2.66 677 1TNK bovine trypsin –2.02 720 1TNI bovine trypsin –2.30 834 1TNL bovine trypsin –2.54 1360 1TNG bovine trypsin –3.98 923 1TNH bovine trypsin –4.57 972 3PTB bovine trypsin –6.43 1634 1PPH bovine trypsin –8.04 2663 1CX9 tryptophan syntethase –9.58 2595 1C29 tryptophan syntethase –9.00 2793 1C9D tryptophan syntethase –8.97 3094 1CW2 tryptophan syntethase –8.76 3094 1C8V tryptophan syntethase –8.92 2571 2TRS tryptophan syntethase –7.20 2646 1QOP tryptophan syntethase –7.20 2721 1A50 tryptophan syntethase –8.56 2914 2TSY tryptophan syntethase –4.65 905 <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006