Table 1.
Structures mapped and additional ligand-bound structures considered
| Target Name | PDB ID | Chains | Drug Class | Hot Spot Structure | Na | MW < 500 | MW > 500 | Hot Spots utilized by ligands | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Nb | Nhac | Nb | Nhac | |||||||
| HIV-1 Protease / Saquinavir | 3OXC | A B | eRo5 | Complex I | 327 | 12 | 6 | 315 | 272 | 0(21), 1 (18), 2(18), 3(13), 4(11), 5(8), 6(5) |
| Heat Shock Protein 90 / PU-1471 | 2FWZ | A | eRo5 | Complex I | 155 | 147 | 58 | 8 | 6 | 0 (25), 1 (21), 2 (16), 4 (6), 5 (6), 6 (5) |
| Thrombin / Argatroban | 1DWC | H | bRo5 | Complex I | 150 | 109 | 65 | 41 | 30 | 0(26), 2(14), 5(6), 6(6), 7(5) |
| MAP Kinase P38 / PF03715455 | 2YIS | A | bRo5 | Complex I | 144 | 117 | 66 | 27 | 22 | 0(26), 1 (21), 2(10), 3(7) |
| Bromodomain BRD4 / Fedratinib | 4OGJ | A B | eRo5 | Complex I | 113 | 103 | 19 | 10 | 4 | 0(21), 1 (18), 2(11), 3(8), 4(8), 5(7), 6(5), 7(5) |
| Renin / Aliskiren | 2V0Z | C | eRo5 | Complex I | 62 | 36 | 20 | 26 | 24 | 0 (24), 1 (15), 2 (12), 3 (8), 4 (8), 5 (7), 6 (7) |
| PPAR-γ / AMG-131 | 3FUR | A | eRo5 | Complex I | 52 | 40 | 10 | 12 | 11 | 2 (9), 4 (8), 5 (8), 6 (7), 8 (6) |
| MAP Kinase Kinase / Cobimetinib | 4AN2 | A | eRo5 | Complex I | 25 | 18 | 11 | 7 | 7 | 0(18), 1 (17), 2(14), 3(13), 4(13) |
| E3 ubiquitin-protein ligase XIAP / Birinapant | 4KMP | A B | bRo5 | Complex I | 20 | 13 | 2 | 7 | 4 | 0(18), 1 (16), 2(16), 3(11), 4(11), 5(7) |
| Epidermal Growth Factor Receptor / Lapatinib | 1XKK | A | eRo5 | Complex II | 59 | 47 | 38 | 12 | 10 | 0 (16), 1 (15), 2 (12), 3 (9), 5 (7), 6 (7) |
| Hepatocyte Growth Factor Receptor / BMS-777607 | 3F82 | A | eRo5 | Complex II | 54 | 36 | 32 | 18 | 16 | 0 (14), 1 (12), 2 (11), 3 (10), 4 (9), 5 (8), 7 (6) |
| Anaplastic Lymphoma Kinase / Ceritinib | 4MKC | A | eRo5 | Complex II | 32 | 23 | 21 | 9 | 7 | 0 (24), 3 (8), 5 (6), 6 (6), 7 (5) |
| Tyrosine Protein Kinase ABL1 / Nilotinib | 3CS9 | A | eRo5 | Complex II | 28 | 18 | 16 | 10 | 9 | 0(20), 2(15), 3(14), 4(13) |
| VEGFR-2 / Nintedanib | 3C7Q | A | eRo5 | Complex II | 24 | 16 | 11 | 8 | 7 | 0 (20), 1 (17), 2 (10), 3 (9), 4 (8), 6 (8), 7 (6) |
| Polo-like Kinase 1 / Volasertib | 3FC2 | A | eRo5 | Complex II | 11 | 4 | 3 | 7 | 6 | 0(28), 1 (19), 2(12), 3(7), 7(5) |
| Glucocorticoid Receptor / Mometasone furoate | 4P6W | A | eRo5 | Complex II | 9 | 6 | 6 | 3 | 3 | 0 (25), 1 (21), 2 (13), 3 (7), 4 (7), 5 (6) |
| Cyclophilin A / Cyclosporine A | 1CWA | A | bRo5 | Complex III | 8 | 5 | 0 | 3 | 3 | 0(27), 1 (16), 4(11), 5(6) |
| Bcl-2 / Navitoclax | 4LVT | A | bRo5 | Complex III | 7 | 0 | 0 | 7 | 7 | 0(22), 2(17), 4(10), 5(5) |
| DOT1-like Histone H3 Methyltransferase / EPZ - 5676 | 4HRA | A | eRo5 | Complex III | 5 | 2 | 0 | 3 | 3 | 1 (17), 2(12), 3(11), 4(6) |
| Lanosterol 14-alpha Demethylase / Itraconazole | 5EQB | A | bRo5 | Complex III | 3 | 2 | 0 | 1 | 1 | 0(23), 1 (17), 2(10), 4(7), 6(5) |
| Isoleucyl-tRNA Synthetase / Pseudomonic Acid A | 1QU2* | A | eRo5 | Complex III | 2 | 0 | 0 | 2 | 1 | 0 (14), 1 (14), 2 (14), 3 (11), 4 (8), 7 (5) |
| FK506 Binding Protein / Rapamycin | 4DRI | A B | bRo5 | Complex III | 2 | 0 | 0 | 2 | 2 | 0 (27), 1 (20), 2 (16), 3 (13), 4 (6), 5 (5) |
| Toll-like Receptor 4 / Eritoran | 2Z65 | C | bRo5 | Complex III | 1 | 0 | 0 | 1 | 1 | 0 (22), 1 (20), 2 (13), 3 (12), 4 (10), 5 (8), 6 (5), 7 (5) |
| FGFR 1 / BGJ-398 | 3TT0 | B | eRo5 | Complex III | 1 | 0 | 0 | 1 | 1 | 0(18), 1 (17), 3(12), 5(6), 6(5) |
| Phosphoinositide-3 Kinase / Pictilisib (GDC-0941) | 3DBS | A | eRo5 | Simple | 65 | 53 | 36 | 12 | 10 | 4 (8) |
| Soluble Acetylcholine Receptor / Tubocurarine | 3PMZ | D E | eRo5 | Simple | 36 | 27 | 10 | 9 | 8 | 0 (19), 3 (13), 5 (9) |
| Protein Farnesyltransferase / Lonafanib | 1O5M | A B | eRo5 | Simple | 34 | 17 | 15 | 17 | 13 | 0 (19), 2 (15) |
| Kinesin Eg5 / Ispinesib | 4A5Y | A | eRo5 | Simple | 28 | 24 | 12 | 4 | 3 | 0 (17), 2 (17), 3 (12) |
| HMG-CoA Reductase / Atorvastatin | 1HWK | A B | eRo5 | Simple | 19 | 6 | 5 | 13 | 13 | 0 (13), 1 (13), 6 (6) |
| Hepatitis C Virus NS5b Subunit / Beclabuvir | 4NLD | A | eRo5 | Simple | 8 | 4 | 3 | 4 | 4 | 2 (10) |
| Hepatitis C Virus NS34A Protease / Simeprevir | 3KEE | A E | bRo5 | Simple | 5 | 0 | 0 | 5 | 5 | 1 (16), 3 (10) |
| DNA-directed RNA-polymerase / Rifampicin | 4KMU* | C | bRo5 | Simple | 3 | 0 | 0 | 3 | 3 | 0 (17) |
| Tubulin-Alpha Chain / Paclitaxel | 1JFF | B | bRo5 | Simple | 2 | 0 | 0 | 2 | 1 | 2 (16), 5 (8) |
| Integrin Aplha-IIB / Eptifibatide | 2VDN* | B | bRo5 | Simple | 2 | 1 | 0 | 1 | 0 | 2 (17) |
| Smoothened Homolog / Taladegib | 4JKV* | A | eRo5 | Simple | 1 | 0 | 0 | 1 | 1 | 0 (20), 1 (19), 3 (12) |
| Na-K ATPase / Ouabain | 3A3Y | A | bRo5 | Simple | 1 | 0 | 0 | 1 | 1 | 1 (17), 2 (12), 3(8) |
| α-Amylase / 3-Acarbose | 1PPI | A | bRo5 | Simple | 1 | 0 | 0 | 1 | 0 | 0 (18), 1 (16), 3 (11) |
*
Indicates domain splitting was performed prior to FTMap (see Methods)
a
N number of structures with bound ligand and known binding affinity;
b
N number of ligand-bound structures
c
NHA number of high affinity structures with bound ligand for the <500 Da and >500 Da cases