Table 1.
Molecular docking results: the results of molecular docking studies of MM compounds and reference ligands against macromolecular structures of proteins involved in the DDR pathway. The common binding residues for MM compounds and reference ligands are bolded.
| MM Compound | Binding Energy (Kcal/mol) |
Binding Residues | Reference Ligand |
Binding Energy (Kcal/mol) |
Binding Residues |
|---|---|---|---|---|---|
| APE-1 DNA-(apurinic or apyrimidinic site) endonuclease 6MKO | |||||
| MM134 | −9.18 | Asp308, His309, Gly176, Gly178, Arg177, Ala230, Trp280, Asn174 | Methoxyamine (No native ligand was complexed) |
−5.74 | Asn212, Asp210, His309, Asn68, Asp308, Glu96 |
| MM136 | −8.07 | Gly178, Arg177, Gly176, Asp308, Trp280, His309, Leu282, Phe266 | |||
| MM137 | −9.64 | Asp308, His309, Gly176, Ala230, Trp280, Phe266, Asn212, Tyr171 | |||
| MM139 | −7.63 | Tyr269, Phe266, Met270, Thr268, Ala230, Asn174, Gly231 | |||
| ATR Serine/threonine-protein kinase ATR 4WAF | |||||
| MM134 | −10.06 | Asp933, Ile848, Tyr836, Ile932, Val850, Met922, Trp780, Thr856, His855 | N,N-dimethyl-4-[(6R)-6-methyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl]benzenesulfonamide | −10.62 | Ile848, Ile932, Val850, Val851, Met922, Glu849, Thr856, His855, Gln859, Lys802, Met800 |
| MM136 | −10.32 | Tyr836, Ile932, Val850, Arg852, Val851, Met922, Asn853, Ser854, Trp780 | |||
| MM137 | −10.95 | Tyr836, Val851, Met922, Val850, Ile932, Trp780, Ser854, Arg852 | |||
| MM139 | −10.34 | Ile848, Ile932, Val850, Trp780, Thr856, His855 | |||
| ATM Serine/threonine-protein kinase ATR 7NI5 | |||||
| MM134 | −9.02 | Pro2775, Gln2874, Trp2769, Leu2767, Leu2715, Ile2888, Tyr2755 | KU-55933 | −10.58 | Tyr2755, Cys2770, Glu2768, Leu2767, Lys2717, Trp2769, Leu2715, Pro2699, Ala2693, Pro2775, Leu2877 |
| MM136 | −9.17 | Asp2720, Lys2717, Leu2877, Trp2769, Thr2773, Cys2770, Tyr2755, Leu2767, Ile2888, Asn2697 | |||
| MM137 | −9.16 | Ala2693, Glu2778, Ile2888, Lys2717, Tyr2755, Leu2767, Cys2770, Trp2769, Leu2877, Pro2775, Val2774 | |||
| MM139 | −10.05 | Trp2769, Leu2877, Tyr2755, Ile2888, Gly2694, Pro2699, Leu2715, Cys2770 | |||
| CHK1 Serine/threonine-protein kinase Chk1 2YM8 | |||||
| MM134 | −9.75 | Cys87, Ala36, Leu137, Leu15, Val23, Leu84, Lys38, Phe149 | (R)-5-(8-chloroisoquinolin-3-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile | −9.14 | Ala36, Leu84, Glu85, Val68, Lys38, Glu134, Asn135, Leu137, Val23, Cys87, Tyr86, Leu15 |
| MM136 | −10.44 | Cys87, Tyr86, Leu137, Leu84, Ala36, Val68, Phe149, Lys38, Val23, Gly90 | |||
| MM137 | −10–82 | Cys87, Ala36, Leu137, Val23, Val68, Lys38, Leu84, Phe149, Asn59, Tyr86 | |||
| MM139 | −10.61 | Cys87, Phe149, Lys38, Val23, Ala36, Leu137, Leu15 | |||
| CHK2 Serine/threonine-protein kinase Chk2 2W0J | |||||
| MM134 | −9.72 | Leu301, Lys249, Asn352, Ile299, Glu308, Val234, Leu354, Leu226 | 4,4′-diacetyldiphenylurea-bis(guanyl-hydrazone) | −9.76 | Glu273, Thr367, Ile299, Lys249, Leu301, Val234, Leu303, Leu226, Glu305 |
| MM136 | −9.64 | Leu226, Met304, Ala247, Leu301, Ile299, Lys249, Thr367, Leu354, Val234 | |||
| MM137 | −9.72 | Leu226, Met304, Ala247, Val234, Leu354, Lys249, Leu301, Ile299 | |||
| MM139 | −10.23 | Phe369, Lys249, Ala247, Leu354, Leu226, Met304, Leu303, Val234, Thr367 | |||
| PARP-1 Poly [ADP-ribose] polymerase 1 7ONS | |||||
| MM134 | −10.51 | Glu763, Tyr889, Asp766, Ala880, Leu877, Arg878, Leu769, Pro881, Tyr896 | 7-[[4-(1,5-dimethylimidazol-2-yl)piperazin-1-yl]methyl]-3-ethyl-1~{H}-quinolin-2-one | −10.36 | Gly863, Arg878, Leu769, Pro881, Asp770, Asn767, Tyr896, Tyr907, Lys903, His862, Ala898 |
| MM136 | −9.88 | Tyr907, His862, Asp766, Asp770, Leu877, Ile872, Arg878, Ala880 | |||
| MM137 | −10.29 | Arg878, Ala898, Tyr907, Tyr896, His862, Ile879 | |||
| MM139 | −10.36 | Ala880, Leu769, Pro881, Arg878, Asn767, Arg865, His909, Tyr907, His862, Asp770 | |||
| RPA70 Replication protein A 70 kDa DNA-binding subunit 4IJL | |||||
| MM134 | −5.81 | Arg41, Ile95, Ile83 | {[5-(3-chloro-1-benzothiophen-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid | −5.97 | Leu87, Met57, Arg41, Ala59, Thr60, Ile95, Val93, Asn85 |
| MM136 | −6.16 | Met97, Ala59, Gln61, Ile83, Ile95 | |||
| MM137 | −5.71 | Arg41, Met92, Ala59, Ile95, Met57, Ile83 | |||
| MM139 | −7.08 | Met57, Ile95, Ile83 | |||
| TOP1 Topoisomerase I 1TL8 | |||||
| MM134 | −9.81 | Met428, Asn352, Lys436, Arg364, Lys425, Thrr426, DA13, DA14 | 2,3-dimethoxy-12H-[1,3]dioxolo[5,6]indeno[1,2]isoquinolin-6-ium | −9.53 | Asn722, Thr718, Arg364, DT10, DG12, DA13 |
| MM136 | −10.44 | Lys425, Arg364, Glu356, Asn722, DT10, DG12, DA13 | |||
| MM137 | −10.69 | Lys425, Lys374, Arg364, DT10, DG12, DA13 | |||
| MM139 | −10.34 | Lys532, DT10 | |||
| TOP2B Topoisomerase II 3QX3 | |||||
| MM134 | −8.54 | Glu477, Gly478, DC8, DA12, DG13 | Etoposide | −9.98 | Asp479, Arg503, Gly478, Met782, DC8, DA12, DG13 |
| MM136 | −8.24 | Arg503, Ala779, Met782, DA12, DG13 | |||
| MM137 | −8.32 | Ser480, Leu502, Asp559, Asp557 | |||
| MM139 | −7.76 | Gly478, Arg503, DC8, DA12, DG13 | |||
| WEE1 Wee1-like protein kinase 2IN6 | |||||
| MM134 | −9.14 | Asp386, Ile305, Cys379, Phe433, Val313, Ala326, Ser307 | PD311839 | −9.45 | Gly382, Cys379, Phe433, Ala326, Glu377, Val313, Val360, Asn376, Lys328, Ile305, Gly306, Ser307 |
| MM136 | −9.99 | Cys379, Asn376, Ile374, His350, Gly382, Val313, Ala326, Phe433, Val360, Lys328, Asp463 | |||
| MM137 | −10.07 | Ile305, Val313, Lys328, Asp463, Ile374, Asn376, Phe433, Val360, Ala326, Cys379 | |||
| MM139 | −9.92 | Lys328, Val313, Ala326, Phe433, Ile305, Tyr378, Gly382, Ser383 | |||