Table 2.
Overview of the MD-derived energetic descriptors and the functional descriptors of AKR1C1 variants. IEP-hP is the interaction energy between protein and hPGS, IEN-hP is the interaction energy between NADP+ and hPGS. The novel L213Q variant is highlighted in grey, ↓ and ↑ represent values lower and higher than the WILD-TYPE, respectively.
| Variant | IEP-hP (kJ/mol) | IEP-hP (kJ/mol) | Km (μM) | kcat (min−1) | kcat/Km (min−1 μM−1) |
|---|---|---|---|---|---|
| R304L | −119.28 ± 81.07 | −31.77 ± 8.89 | 283.3 ± 13.2 | 96.1 | 0.3 ↓ |
| E127D | −97.50 ± 63.49 | −14.29 ± 9.22 | 9.4 ± 2.5 | 4.4 | 0.4 ↓ |
| H222I | −111.04 ± 67.84 | −28.61 ± 8.76 | 28.6 ± 5.2 | 18.5 | 0.6 ↓ |
| H222S | −110.99 ± 68.25 | −8.57 ± 5.19 | 25.6 ± 5.7 | 39.6 | 1.5 ↓ |
| L213Q | −114.93 ± 24.89 | −8.90 ± 6.87 | 5.1 | 38.2 | 7.55 ↓ |
| T307V | −126.19 ± 70.32 | −33.38 ± 7.61 | 4.1 ± 0.3 | 41.3 | 10 ↓ |
| WILD-TYPE | −118.72 ± 13.23 | −5.69 ± 7.10 | 4.2 ± 0.8 | 65.1 | 15.2 |
| D309L | −126.98 ± 83.16 | −19.78 ± 10.08 | 4.6 ± 0.6 | 119.5 | 25.9 ↑ |
| Y305F | −120.12 ± 84.75 | −19.72 ± 6.08 | 5.6 ± 1.9 | 156.3 | 27.9 ↑ |