## 3 Results
### 17\(\beta\)-HSD1 (17\(\beta\)-Hydroxysteroid Dehydrogenase)  
We examined the X-ray crystal structures of Estradiol 17\(\beta\)-dehydrogenase 1 (17\(\beta\)-HSD1) deposited in the PDB database and selected 15 human X-ray structures available (resolution = 1.5-3.5 A). From these (Figure 15), PDB entry 3 KLM was chosen to perform the docking since it contains 5\(\alpha\)-dihydrotestosterone (ID: DHT), which partially resembles ceruchinol (see Figure 16).  
Figure 16: Chemical structure of (**left**) ceruchinol and (**right**) 5\(\alpha\)-dihydrotestosterone (ID: DHT).  
Figure 14: (**Left**). Result of the control docking simulation. The co-crystallized ligand is shown in orange and the redocked ligand is shown in yellow. (**Right**) Result of the docking simulation of ceruchinol. Pose 1 is shown in green and pose 2 is shown in cyan.  
Figure 15: Superposition of the selected 17\(\beta\)-HSD1 structural models. Co-crystallized ligands are shown in orange. The 15 structures are shown to demonstrate that the binding site is the same for all of them, as well as the alignment of the structures.  
The result of the docking of DHT and ceruchinol are shown in Figure 17 (top left and right images). Notably, the PDB structure 3 KLM shows two alternative binding modes for DHT. This suggests that the natural ligand is not able to establish specific interactions with the target protein, and binding is mainly guided by size and shape complementarity. Therefore, the fact that docking does not reproduce accurately the X-ray binding mode is not surprising. Indeed, the first binding mode is mimicked by pose 4 (Figure 17 down left) and the second arrangement by pose 9 (Figure 17 down right). In both cases, the control ligand does not exactly overlay the X-ray structure, but the poses are acceptable. The energies and docking score calculated for the redocking simulation are reported in Table 4.  
Docking of ceruchinol generated two putative poses, each of which is partially superimposed to the two X-ray orientations of DHT (see Figure 17 and Table 4). The binding mode of ceruchinol features the same pattern of non-polar interactions as DHT, but also tends to form an additional H-bond with a vicinal Tyr residue (Tyr218 in pose 1 and Tyr155 in pose 2). Nevertheless, the formation of this interaction should be taken with caution on  
\begin{table}
\begin{tabular}{l c c c c} \hline \hline  & \multicolumn{2}{c}{**Total Energy**} & \multicolumn{2}{c}{**Interaction Energy**} & \multicolumn{2}{c}{**Docking Score**} \\  & **(kcal/mol)** & **(kcal/mol)** & **(kcal/mol)** \\ \hline \multirow{2}{*}{Ligand DHT} & Pose 4 & 61.8 & \(-\)23.4 & \(-\)8.7 \\ \cline{2-5}  & Pose 9 & 62.7 & \(-\)22.2 & \(-\)8.1 \\ \hline \multirow{2}{*}{Ceruchinol} & Pose 1 & 31.3 & \(-\)24.3 & \(-\)8.4 \\ \cline{2-5}  & Pose 3 & 33.3 & \(-\)23.4 & \(-\)8.8 \\ \hline \hline \end{tabular}
\end{table}
Table 4: Total energy, interaction energy, and docking score for the simulated poses of ligand DHT and ceruchinol.  
Figure 17: Results of the control docking simulation for (**top left**) the first and (**top right**) the second proposed binding mode and docking simulation of ceruchinol in (**down left**) pose 4 and (**down right**) pose 9. The co-crystallized ligand is shown in orange, the redocked ligand in yellow, and the docking simulation of ceruchinol is shown in green.  
the basis of the X-ray data. Keeping this in mind, we can assume that ceruchinol is a good candidate to be used as an inhibitor modulator for 17\(\beta\)-HSD1.