Binding scores (kJ/mol) and carbonyl to hydride NADP distance (Å) obtained from minimum energy binding poses of known and possible substrates docked into 11β-HSD1 (PD BID: 2BEL) using MOE-Dock (Molecular Operating Environment 2008.10, Chemical Computing group, Montreal, Canada).
In silico predictions of potential 11β-HSD1 substrates are presented based on the range of binding scores and the hydride-carbonyl distance between NADPH and known substrates that flank possible substrate candidates. Structures of reference chemicals can be found in the supplemental information.
Rank | Substrate | Substrate Class | 11β-HSD1 Reactivity | Binding Score | Distance (Å) (O = C-(H)NADP) |
|---|---|---|---|---|---|
| kJ/mol | |||||
| 1 | 15-Deoxy-Δ-12,4-PGJ2 | Natural | Known | -54.3 | 3.3 |
| 2 | Dioxybenzone | Sunscreen | Possible | -54.2 | 3.1 |
| 3 | Biochanin A | Dietary | Possible | -53.6 | 2.7 |
| 4 | Cortisone | Natural | Known | -52.8 | 3.9 |
| 5 | Ticrynafen | Therapeutic | Possible | -52.4 | 2.9 |
| 6 | Tralkoxydim | Pesticide | Possible | -52.4 | 2.8 |
| 7 | 7-Ketocholesterol | Natural | Known | -52.3 | 2.5 |
| 8 | Triadimefon | Pesticide | Known | -51.0 | 2.6 |
| 9 | Irisol Base | Food Additive | Possible | -50.6 | 3.2 |
| 10 | Ketoprofen | Therapeutic | Known | -49.9 | 2.9 |
| 11 | Warfarin | Therapeutic | Possible | -49.4 | 3.1 |
| 12 | Oracin | Therapeutic | Known | -48.3 | 3.1 |
| 13 | Ketanserin | Therapeutic | Possible | -45.7 | 3.2 |
| 14 | Metyrapone | Therapeutic | Known | -39.3 | 2.6 |
| 15 | Menadione | Vitamin K2 | Known | -37.0 | 3.2 |