Table 5.
Virtual screening (obtained by AutoDock VINA), molecular docking (obtained by AutoDock 4.2.6) results and ROC probability of compounds binding to 2′-o-ribose-methyltransferase. Details see Table 3.
| Dataset | ROC probability | VINA defined LBE | AutoDock defined LBE | Interacting amino acid residues |
|---|---|---|---|---|
| FDA approved drugs: | ||||
| Conivaptan | 1.000 | −10.83 ± 0.06 | −10.94 ± 0.38 | Trp6803, Gln6804, Gln6850, Asn6853, Tyr7040, Ser7041, Asp7044 |
| Lifitegrast | 1.000 | −10.57 ± 0.11 | −10.88 ± 0.23 | Trp6803, Asn6853, Tyr7040, Lys7047, Lys7051 |
| Dihydroergotamine | 1.000 | −12.17 ± 0.05 | −9.56 ± 0.41 | Ser6903, Ala6905, Asp6906, Ser6907, Ser7090, Val7092 |
| Ergotamine | 1.000 | −12.30 ± 0.10 | −9.46 ± 0.07 | Leu6892, Ala6905, Asp6906, Ser6907, Thr6908, Val7086, Val7087 |
| Eltrombopag | 0.999 | −11.03 ± 0.05 | −9.19 ± 0.34 | Lys6933, Thr6934, Asn6936, Lys6939, Lys6944, Glu6945 |
| Ponatinib | 1.000 | −10.47 ± 0.12 | −9.17 ± 0.29 | Ser7039, Trp6803, Thr6833, Leu7037, Tyr7040, Phe7043 |
| Lumacaftor | 0.999 | −11.13 ± 0.05 | −8.75 ± 0.08 | His6972, Lys6933, Thr6934, Asn6936, Lys6939, Ser6943, Glu6945 |
| Nilotinib | 1.000 | −11.30 ± 0.10 | −8.43 ± 0.34 | Asp6931, Lys6939, Ser6943, Lys6944, Glu6945, Ser6973, Tyr7020 |
| Regorafenib | 1.000 | −10.50 ± 0.10 | −7.98 ± 0.33 | Tyr7040, Trp6803, Gln6850, Asn6853, Ser7041, Lys7047 |
| Aprepitant | 1.000 | −10.63 ± 0.05 | −6.25 ± 0.42 | Ser6800, Trp6803, Gln6804, Pro6805, Gln6850, Asp7044 |
| Natural compounds from literature: | ||||
| Loniflavone | 1.000 | −10.80 ± 0.10 | −9.69 ± 0.09 | Asp6897, Lue6898, Cys6913, Met6929, Tyr6930, Asp6931, Ser6943, Glu6945 |
| Friedelin | 1.000 | −9.73 ± 0.06 | −8.95 ± 0.02 | Thr6833, Leu7037, Ser7039, Tyr7040, Phe7043 |
| TingeninB | 0.999 | −10.47 ± 0.06 | −8.75 ± 0.10 | Tyr6803, Gln6804, Gln6850, Tyr7040, Asp7044, Lys7047 |
| Hoslunddiol | 1.000 | −9.60 ± 0.10 | −7.12 ± 0.09 | Tyr7040, Ser6800, Trp6803, Gln6804, Pro6805, Asp7044, Ser7041 |
| Wogonoside | 1.000 | −9.57 ± 0.11 | −6.18 ± 0.16 | Asp6931, Thr6934, Lys6939, Sdp6942, Ser6943, Glu6945, Gly6946 |
| Procyanidin | 1.000 | −9.70 ± 0.10 | −5.98 ± 0.49 | Asn6936, Asp6931, Lys6933, Val6937, Thr6938, Glu6940, Lys6939 |
| Baicalin | 1.000 | −9.80 ± 0.10 | −5.95 ± 0.22 | Lys7075, Leu7010, Arg7014, Ser7074 |
| IlexsaponinB2 | 1.000 | −9.47 ± 0.12 | −4.25 ± 0.03 | Lys7075, Pro6810, Asn6811, Tyr6851, Thr6854, Leu6855, Trp6987, Lys7075 |
| Punicalagin | 1.000 | −9.43 ± 0.15 | −2.45 ± 0.04 | Ile7088, Leu6892, Asp6906, Ser6907, Thr6908, Arg7085, Val7087 |
| TirucallinA | 1.000 | −10.17 ± 0.06 | 0.25 ± 0.06 | Asn6862, Arg6864, Leu6892, Asp6906, Ser6907, Val7086 |
| Natural compounds from ZINC database: | ||||
| ZINC000015675938; (6S)–N-(4-chlorophenyl)-6-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]-1H,4H,5H,6H,7H-imidazo [4,5-c]pyridine-5-carboxamide | 1.000 | −12.03 ± 0.21 | −12.04 ± 0.07 | Asp6931, Thr6934, Asn6936, Val6937, Thr6938, Lys6939, Glu6940, Asp6942, Lys6944, Glu6945, Gly6946, Phe6947, Ser6973 |
| ZINC000004258894; N-[(1R,9S)-11-{[1,1′-biphenyl]-4-carbonyl}-6-oxo-7,11-diazatricyclo [7.3.1.02,⁷]trideca-2,4-dien-5-yl]-2-phenylacetamide | 1.000 | −12.09 ± 0.10 | −11.86 ± 0.05 | Thr6833, Ser7038, Ser7039, Tyr7040, Ser7041, Phe7043, Asp7044 |
| ZINC000004259861; 3-[(3S,3aR,6S,6aR)-6-{5-[4-(1H-1,2,4-triazol-1-yl)phenoxy]-1H-1,2,3,4-tetrazol-1-yl}-hexahydrofuro [3,2-b]furan-3-yl]-1-(4-phenoxyphenyl)urea | 1.000 | −12.11 ± 0.09 | −11.84 ± 0.07 | Trp6803, Asp6830, Ser6831, Thr6833, Leu7037, Ser7038, Ser7039, Tyr7040, Phe7043 |
| ZINC000004259794; N-[(3S,3aR,6S,6aR)-6-[5-(2H-1,3-benzodioxol-5-yloxy)-1H-1,2,3,4-tetrazol-1-yl]-hexahydrofuro [3,2-b]furan-3-yl]naphthalene-2-sulfonamide | 1.000 | −12.13 ± 0.12 | −11.31 ± 0.09 | Trp6803, Ala6832, Thr6833, Leu7037, Ser7038, Ser7039, Tyr7040, Phe7043 |
| ZINC000008635475; N-[4-()[(2R,4S,5R)-5-[1-methyl-3-(naphthalen-2-yl)-1H-pyrazol-5-yl]-1-azabicyclo [2.2.2]octan-2-yl]methyl)sulfamoyl)phenyl]acetamide | 1.000 | −12.27 ± 0.15 | −11.24 ± 0.06 | Lys6939, Glu6940, Asp6942, Ser6943, Lys6944, Glu6945, Asp7018, Tyr7020 |
| ZINC000004259775; 3-[(3S,3aR,6S,6aR)-6-[5-(2H-1,3-benzodioxol-5-yloxy)-1H-1,2,3,4-tetrazol-1-yl]-hexahydrofuro [3,2-b]furan-3-yl]-1-(naphthalen-1-yl)urea | 1.000 | −12.37 ± 0.21 | −11.16 ± 0.13 | Gly6869, Gly6871, Asp6897, Asp6912, Cys6913, Asp6928, Tyr6930, Asp6931, Lys6944, Glu6945, Gly6946, Phe6947 |
| ZINC000253407092; 4-[3-((4,5-bis [(4,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy]-6-methyltetrahydro-2H-pyran-2-yl)oxy)-14,16-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta [a]phenanthren-17-yl]-2(5H)-furanone | 1.000 | −12.40 ± 0.30 | −11.13 ± 0.10 | Gly6869, Ser6872, Asp6897, Leu6898, Asn6899, Met6929, Tyr6930, Asp6931, Pro6932, Lys6933, Thr6934, Ser6943, Lys6944, Glu6945, Gly6946, Phe6947 |
| ZINC000253504766; 3-[(3S,5S,8S,9R,10S,12R,13S,14S,17S)-3-[(2S,4R,5R,6R)-5-[(2R,4R,5R,6R)-5-[(2S,4R,5S,6R)-4,5-Dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta [a]phenanthren-17-yl]-2H-furan-5-one | 1.000 | −12.43 ± 0.15 | −10.82 ± 0.60 | Ser6872, Asp6873, Asp6897, Leu6898, Asn6899, Met6929, Tyr6930, Asp6931, Pro6932, Lys6939, Lys6944, Glu6945, Gly6946, Phe6947, Phe6948 |
| ZINC000253504770; 4-(7-)[5-()5-[(4,5-dihydroxy-6-methyloxan-2-yl)oxy]-4-hydroxy-6-methyloxan-2-yl)oxy)-4-hydroxy-6-methyloxan-2-yl]oxy)-3a,11-dihydroxy-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta [a]phenanthren-1-yl)-2,5-dihydrofuran-2-one | 1.000 | −12.47 ± 0.12 | −10.64 ± 0.16 | Tyr6828, Gly6829, Asp6830, Ser6831, Thr6833, Leu7037, Ser7039, Tyr7040, Phe7043 |
| ZINC000253500684; 4-[(7S,9aS,11aR)-3a-hydroxy-7-[(4-methoxy-6-methyl-5-{[3,4,5-trihydroxy-6-({[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl]oxy}oxan-2-yl)oxy]-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta [a]phenanthren-1-yl]-2,5-dihydrofuran-2-one | 1.000 | −11.98 ± 0.24 | −8.23 ± 0.10 | Ala6808, Tyr6851, Leu6855, Thr6856, Trp6987, Leu7010, Asp7067, Leu7070, Ser7071, Ser7074, Lys7075 |