Table 3.
PIEDA of the five amino acids in the membrane-binding domain of COX-2.
| Compound Name | Amino Acid | Pair Interaction Energy (kcal/mol) |
Component of Pair Interaction Energy (kcal/mol) c | ||||
|---|---|---|---|---|---|---|---|
| ES | EX | CT | DI | SL | |||
| Chemocoxib A a | Lys79 | −15.267 | −1.364 | −0.126 | −0.195 | −5.647 | −7.936 |
| Lys83 | −10.241 | −2.342 | 0.303 | −0.257 | −3.839 | −4.105 | |
| Tyr122 | −6.049 | 0.502 | 0.104 | 0.000 | −6.321 | −0.334 | |
| Leu117 | −3.464 | −3.101 | 0.001 | 0.000 | −0.565 | 0.201 | |
| Val89 | −3.267 | 0.018 | −0.072 | −0.002 | −3.200 | −0.012 | |
| Kuwanon A b | Lys79 | −1.807 | −2.344 | 0.000 | 0.000 | −0.531 | 1.068 |
| Lys83 | −14.430 | −7.995 | 0.782 | −0.152 | −8.657 | 1.591 | |
| His122 | −0.830 | −0.825 | 0.000 | 0.000 | −0.258 | 0.253 | |
| Leu117 | −0.934 | −1.120 | 0.756 | −0.022 | −0.609 | 0.061 | |
| Val89 | −6.599 | −0.771 | 0.532 | −0.016 | −6.172 | −0.172 | |
| Kuwanon B b | Lys79 | −1.468 | 0.839 | 0.000 | 0.000 | −0.037 | −2.271 |
| Lys83 | −1.721 | 4.021 | 0.000 | 0.000 | −0.503 | −5.239 | |
| His122 | −0.096 | 0.069 | 0.000 | 0.000 | −0.051 | −0.114 | |
| Leu117 | −0.024 | −0.103 | 0.000 | 0.000 | −0.370 | 0.449 | |
| Val89 | −4.665 | 1.035 | 0.217 | −0.011 | −4.866 | −1.040 | |
| Kuwanon C b | Lys79 | −3.164 | 0.158 | −0.003 | 0.000 | −1.035 | −2.285 |
| Lys83 | −14.541 | −7.330 | 3.374 | −0.198 | −7.612 | −2.775 | |
| His122 | −0.830 | −0.825 | 0.000 | 0.000 | −0.258 | 0.253 | |
| Leu117 | −0.934 | −1.120 | 0.756 | −0.022 | −0.609 | 0.061 | |
| Val89 | 4.212 | −0.154 | 8.521 | −0.128 | −3.934 | −0.091 | |
| Kuwanon E b | Lys79 | −2.662 | −5.799 | 0.000 | 0.000 | −0.382 | 3.518 |
| Lys83 | −8.604 | −3.086 | 0.050 | −0.001 | −5.367 | −0.200 | |
| His122 | −1.933 | −1.678 | −0.001 | 0.000 | −0.775 | 0.521 | |
| Leu117 | −0.199 | −0.139 | 0.000 | 0.000 | −0.351 | 0.291 | |
| Val89 | −5.810 | −0.328 | 0.563 | −0.023 | −5.754 | −0.267 | |
| Kuwanon H b | Lys79 | −3.997 | −0.092 | 0.000 | 0.000 | −0.434 | −3.471 |
| Lys83 | −10.573 | −6.387 | 1.361 | −0.033 | −4.870 | −0.645 | |
| His122 | −0.515 | −0.150 | 0.000 | 0.000 | −0.088 | −0.277 | |
| Leu117 | 1.646 | 2.200 | 0.000 | 0.000 | −0.349 | −0.205 | |
| Val89 | −6.257 | 0.117 | 0.334 | −0.002 | −6.521 | −0.185 | |
a Pair interaction energy of chemocoxib A represents the interaction energy between podophyllotoxin and linker structures and murine COX-2 (PDB ID: 4OTJ). b Pair interaction energy of kuwanon derivatives represent the interaction energy between the kuwanon derivatives and human COX-2 (5IKR). c ES: ElectroStatic interaction, EX: EXchanged repulsion, CT: Charge Transfer, DI: Dispersion, SL: SoLvation. The bold amino acid is located in entrance/exit routes of COX-2 active sites.