Table 6.
Binding energy of ligands and positive controls on MAPK signaling pathway.
| Grid Box | Hydrogen Bond Interactions | Hydrophobic Interactions |
|||||
|---|---|---|---|---|---|---|---|
| Protein | Ligand | PubChem ID | Binding Energy (kcal/mol) |
Center | Dimension | Amino Acid Residue | Amino Acid Residue |
| FGF1 (PDB ID:3OJ2) |
(★) Campesterol | 173183 | −8.4 | x 9.051 | x 40 | Asp283, Ser252 | Arg251,Phe172, Ile257 |
| y 22.527 | y 40 | Ser220, Leu258, Ile204 | |||||
| z −0.061 | z 40 | Ala260, Gln259, Tyr281 | |||||
| 3,4-O-Isopropylidene-d-galactose | 54504880 | −6.1 | x 9.051 | x 40 | Arg255, Thr174, Phe172 | Asn350, Asn173, Ala349 | |
| y 22.527 | y 40 | Asn107, Gln348 | |||||
| z −0.061 | z 40 | ||||||
| Positive control | (a) Suramin sodium | 8514 | −19.1 | x 9.051 | x 40 | Ser282, Lys27 | Arg203, Ile204, Ala260 |
| y 22.527 | y 40 | Gln259, Leu258, Tyr281 | |||||
| z −0.061 | z 40 | Asn22, Tyr23, Asp283 | |||||
| Val249, Pro149, Glu250 | |||||||
| His254, Ser252, Ile257 | |||||||
| Phe172, Val222, Ser220 | |||||||
| FGF2 (PDB ID:1IIL) | (★) 26,27-Dinorergosta-5,23-dien-3β-ol | 22213488 | −8.0 | x 26.785 | x 40 | Thr139, Ser137 | Glu323, Ser122, Trp123 |
| y 14.360 | y 40 | Lys313, Leu312, Ile329 | |||||
| z −1.182 | z 40 | Leu327, Tyr328 | |||||
| Campesterol | 173183 | −7.9 | x 26.785 | x 40 | Ser137 | Thr139, Glu323, Lys313 | |
| y 14.360 | y 40 | Asp336, Tyr328, Ile329 | |||||
| z −1.182 | z 40 | Leu312, Leu327, Ser122 | |||||
| Trp123, Thr319 | |||||||
| Stigmasta-5,22-dien-3-ol | 53870683 | −7.8 | x 26.785 | x 40 | Tyr340, Asp336 | Ile329, Leu312, Ser122 | |
| y 14.360 | y 40 | Trp123, Ser137, Thr319 | |||||
| z −1.182 | z 40 | Glu323, Asn318, Lys313 | |||||
| Leu327 | |||||||
| 3,4-O-Isopropylidene-d-galactose | 54504880 | −5.6 | x 26.785 | x 40 | Glu323, Trp123, Ser137 | Ser122 | |
| y 14.360 | y 40 | Thr139, Lys313 | |||||
| z −1.182 | z 40 | ||||||
| Positive control | (b) NSC172285 | 299405 | −14.7 | x 26.785 | x 40 | Tyr207 | Val209, Asp99, Lys119 |
| y 14.360 | y 40 | Lys199, Gln200, Glu201 | |||||
| z −1.182 | z 40 | ||||||
| (b) NSC37204 | 235612 | −9.5 | x 26.785 | x 40 | Thr358, Arg210, Thr121 | Val209, Asn265, Lys119 | |
| y 14.360 | y 40 | Arg118, Glu201 | Asp99, Gln200, Trp356 | ||||
| z −1.182 | z 40 | ||||||
| VEGFA (PDB ID: 3V2A) | (★) 3,4-O-Isopropylidene-d-galactose | 54504880 | −5.3 | x 38.009 | x 40 | Gly312, Ser310 | Gly255, Glu44, Ser311 |
| y −10.962 | y 40 | Ile256, Asp257, Lys84 | |||||
| z 12.171 | z 40 | Pro85 | |||||
| Glyceryl palmitate | 14900 | −5.2 | x 38.009 | x 40 | Pro40, Asp276 | Arg275, Phe36, Lys286 | |
| y −10.962 | y 40 | Lys48, Asn253, Ile46 | |||||
| z 12.171 | z 40 | ||||||
| Monoolein | 5283468 | −5.1 | x 38.009 | x 40 | Asp276, Pro40 | Arg275, Asp34, Asn253 | |
| y −10.962 | y 40 | Lys48, Phe47, Ile46 | |||||
| z 12.171 | z 40 | Phe36, Lys286 | |||||
| Methyl palmitate | 8181 | −4.0 | x 38.009 | x 40 | n/a | Pro40, Arg275, Phe36 | |
| y −10.962 | y 40 | Ile46, Asn253, Lys286 | |||||
| z 12.171 | z 40 | Asp276 | |||||
| Isopropyl hexanoate | 16832 | −3.9 | x 38.009 | x 40 | n/a | Pro85, Ser310, Gly312 | |
| y −10.962 | y 40 | Glu44, Ser311, Gly255 | |||||
| z 12.171 | z 40 | Gln87, Lys84, Asp257 | |||||
| Positive control | (c) BAW2881 | 16004702 | −7.6 | x 38.009 | x 40 | n/a | Lys286, Asp34, Ser50 |
| y −10.962 | y 40 | Asp276, Pro40, Phe36 | |||||
| z 12.171 | z 40 | Ile46 | |||||
| TNFRSF1A (PDB ID: 1NCF) | (★) CBMicro_013618 | 1109374 | −6.8 | x 21.259 | x 40 | Lys132, Gln133 | Glu109, Tyr106, Gln130 |
| y 14.648 | y 40 | Gln133 | |||||
| z 34.77 | z 40 | ||||||
| 2-Propenoic acid, 3-phenyl-, methyl ester | 7644 | −5.0 | x 21.259 | x 40 | Lys35 | Ala62, Glu64, His34 | |
| y 14.648 | y 40 | Lys35, Glu64 | |||||
| z 34.77 | z 40 | ||||||
| Positive control | (d) Enamine_004209 | 2340496 | −5.3 | x 21.259 | x 40 | Glu109, Cys96, Tyr106 | Asn110, Ph112, Val95 |
| y 14.648 | y 40 | Gln82, Ser74, Thr94 | |||||
| z 34.77 | z 40 | Arg77, Arg132 | |||||
| PLA2G4A (PDB ID: 1BCI) | (★) Stearic acid | 5281 | −4.5 | x −0.058 | x 40 | Gly33, Lys32 | Pro42, Val30, Ile67 |
| y 0.077 | y 40 | Val127, Thr31, Gln126 | |||||
| z 0.285 | z 40 | ||||||
| Methyl palmitate | 8181 | −3.9 | x −0.058 | x 40 | Lys58 | Phe77, Pro54, Thr53 | |
| y 0.077 | y 40 | Leu79, Tyr16, Glu76 | |||||
| z 0.285 | z 40 | Ile78 | |||||
| Palmitic acid | 985 | −3.8 | x −0.058 | x 40 | Thr53 | Leu79, Phe77, Ile78 | |
| y 0.077 | y 40 | Tyr16, Glu76, Pro54 | |||||
| z 0.285 | z 40 | ||||||
| Myristic acid | 11005 | −3.3 | x −0.058 | x 40 | n/a | Asp55, Pro54, Tyr16 | |
| y 0.077 | y 40 | Phe77, Ile78, Thr53 | |||||
| z 0.285 | z 40 | ||||||
| Positive control | (e) Berberine | 2353 | −6.6 | x −0.058 | x 40 | n/a | Arg59, Asp99, Asn95 |
| y 0.077 | y 40 | His62, Phe63, Asn64 | |||||
| z 0.285 | z 40 | Arg61, Ala94, Tyr45 | |||||
| PRKCA (PDB ID: 3IW4) | (★) Monoolein | 5283468 | −6.7 | x −14.059 | x 40 | Asn660, Leu393, Asp395 | Pro398, Lys478, Glu418 |
| y 38.224 | y 40 | Lys396 | Pro666, Tyr419, Arg608 | ||||
| z 32.319 | z 40 | Val664, Gln402 | |||||
| Glyceryl palmitate | 14900 | −6.6 | x −14.059 | x 40 | Asp395, Lys396, Leu393 | Leu394, Gln402, Lys478 | |
| y 38.224 | y 40 | Asn660 | Arg608, Pro666, Ile667 | ||||
| z 32.319 | z 40 | Val664, Pro398, Pro397 | |||||
| Stearic acid | 5281 | −6.3 | x −14.059 | x 40 | Lys396, Leu393 | Pro397, Pro398, Lys478 | |
| y 38.224 | y 40 | Arg608, Ile667, Pro666 | |||||
| z 32.319 | z 40 | His665, Val664, Gln402 | |||||
| Asn660, Leu394 | |||||||
| Nonadecanoic acid | 12591 | −6.2 | x −14.059 | x 40 | Leu393, Lys396 | Asn660, Pro397, Pro398 | |
| y 38.224 | y 40 | Lys478, Pro666, Arg608 | |||||
| z 32.319 | z 40 | Glu418, Val664, Gln402 | |||||
| Leu394 | |||||||
| 1,6,10-Dodecatrien-3-ol, 3,7,11-trimethyl- | 8888 | −6.2 | x −14.059 | x 40 | Lys372, Gln408, Gln650 | Val410, Thr409, Gly540 | |
| y 38.224 | y 40 | Ile645, Asp539, Asp503 | |||||
| z 32.319 | z 40 | Phe538, Glu543 | |||||
| 2,5-Furandione, 3-dodecenyl- | 5362708 | −6.1 | x −14.059 | x 40 | Lys396, Asp395 | Asn660, Gln402, Pro397 | |
| y 38.224 | y 40 | Pro398, Glu552, Gln662 | |||||
| z 32.319 | z 40 | Val664, Leu394 | |||||
| 2,6-Dimethyl-3,5,7-octatriene-2-ol, Z,Z- | 5363692 | −5.3 | x −14.059 | x 40 | Gly540 | Val410, Ile645, Asp503 | |
| y 38.224 | y 40 | Pro502, Glu543, Gln650 | |||||
| z 32.319 | z 40 | Leu546, Asp542 | |||||
| 2-Dodecenoic acid | 5282729 | −5.1 | x −14.059 | x 40 | Lys396, Asn660, Leu393 | Leu394, Gln662, Glu552 | |
| y 38.224 | y 40 | Val664, Gln402 | |||||
| z 32.319 | z 40 | ||||||
| 9-Octadecenoic acid | 965 | −5.0 | x −14.059 | x 40 | Leu393, Lys396 | Asn660, Glu552, Gln548 | |
| y 38.224 | y 40 | His553, Ser549, Gln662 | |||||
| z 32.319 | z 40 | Val664, Gln402, Leu394 | |||||
| Octanoic acid | 379 | −5.0 | x −14.059 | x 40 | Asn660, Lys396, Gln402 | Pro397, Lys478, Pro398 | |
| y 38.224 | y 40 | Val664, Glu552, Arg608 | |||||
| z 32.319 | z 40 | ||||||
| Methyl palmitate | 8181 | −5.0 | x −14.059 | x 40 | n/a | Gln377, Asn647, Asp373 | |
| y 38.224 | y 40 | Ile648, Asp649, Asn468 | |||||
| z 32.319 | z 40 | Lys465, Phe350, Asp467 | |||||
| Ile376 | |||||||
| Palmitic acid | 985 | −5.0 | x −14.059 | x 40 | Leu393, Asp395, Lys396 | Pro397, Pro398, Val664 | |
| y 38.224 | y 40 | Glu552, His553, Ser549 | |||||
| z 32.319 | z 40 | Gln548,Gln662, Gln402 | |||||
| Leu394, Asn660 | |||||||
| (E)-4-Undecenal | 5283357 | −4.8 | x −14.059 | x 40 | n/a | Gln642, Pro536, Ile645 | |
| y 38.224 | y 40 | Gly540, Val410, Gln650 | |||||
| z 32.319 | z 40 | Glu543, Asp542, Asp503 | |||||
| Leu546 | |||||||
| Myristic acid | 11005 | −4.8 | x −14.059 | x 40 | Lys396, Gln402 | Asp395, Leu393, Leu394 | |
| y 38.224 | y 40 | Pro398, Val664, Gln662 | |||||
| z 32.319 | z 40 | Asn660 | |||||
| Nonanoic acid | 8158 | −4.7 | x −14.059 | x 40 | Leu393, Lys396 | Leu394, Asn660, Pro397 | |
| y 38.224 | y 40 | Gln402, Gln662, Val664 | |||||
| z 32.319 | z 40 | ||||||
| Heptadec-8-ene | 520230 | −4.6 | x −14.059 | x 40 | n/a | Asn647, Asp424, Met426 | |
| y 38.224 | y 40 | Gln377,Ile376, Phe350 | |||||
| z 32.319 | z 40 | Asp467, Asp373 | |||||
| Positive control | (f) Sphingosine | 5280335 | −5.5 | x −14.059 | x 40 | Asn660, Gln662, Lys396 | Pro397, Gln402, Val664 |
| y 38.224 | y 40 | Gln548, Glu552, His553 | |||||
| z 32.319 | z 40 | Leu394, Ser549, Asp395 | |||||
(★) Compound with the greatest affinity on each target; (a) FGF1 antagonist; (b) FGF2 antagonist; (c) VEGFA antagonist; (d) TNFRSF1A antagonist; (e) PLA2G4A antagonist; (f) PRKCA antagonist.