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Table 1 Ensemble analysis of the binding sites of protein-protein interaction inhibitors

From: Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets

Protein Binding site size (atoms) Method Percentage of site identified as pocket-lining
    apo structure Provar Score > 0.75 Provar Score > 0.25
   PASS 38 21 64
Bcl-X L 56 LIGSITE 73 69 91
   fpocket 52 36 89
   PASS 46 15 50
MDM2 48 LIGSITE 52 38 77
   fpocket 38 6 45
   PASS 29 26 69
XiapBir3 42 LIGSITE 67 52 98
   fpocket 31 24 83
   PASS 25 16 54
XiapBir3 63 LIGSITE 57 44 87
   fpocket 30 19 74
   PASS 70 35 75
ZipA 20 LIGSITE 35 5 60
   fpocket 0 15 15
   PASS 46 23 54
HPVE2 97 LIGSITE 44 26 56
   fpocket 33 2 53
   PASS 38 7 58
IL2 60 LIGSITE 22 22 62
   fpocket 0 2 2
   PASS 53 53 68
HIV-1 Integrase 19 LIGSITE 37 16 47
   fpocket 68 5 58
   PASS 6 0 29
TNFa 34 LIGSITE 3 0 44
   fpocket 0 0 3
   PASS 0 0 69
TNFR1a 16 LIGSITE 50 38 100
   fpocket 0 0 69
   PASS 62 30 57
MDM4 81 LIGSITE 44 31 68
   fpocket 38 0 42
   PASS 38.5 20.5 59
Mean Values 49 LIGSITE 49 31 72
   fpocket 37.5 8.5 48
  1. Provar analysis of a tCONCOORD generated ensemble of 250 structures of the apo form of each of the 11 proteins in the 2P2I database identifies a greater proportion of the known binding site atoms as pocket-lining than analysis of the crystallographic structure alone. The proportion of inhibitor binding-site atoms found to be persistently or variably lining pockets (defined as pocket-lining in at least 25% of conformers) is significantly greater than for the protein as a whole in 21/33cases. (An italic number in the final column indicates the minority of cases in which the proportion is not significant at the p < 0.05 level). Further details of the structures are given in Table 4.