## 2 Materials and Methods
### In Silico Molecular Docking  
Molecular docking analysis was achieved using a previously described method [27]. All protein target structures were retrieved from the RCSB Protein Data Bank [28] (Table 1). These structures were optimized as suitable docking targets, using Autodock Tools v1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). The protein structure file was prepared by removing water molecules, unlinked atoms/protein chains, and the native ligands after which the potential of the protein target was assigned with Kollman charges, a feature imbedded in the software. The target structures were saved as pdbqt files. The structuresof the 37 RGEO compounds were generated based on their available SMILE strings (or isomeric SMILE strings in case of enantiomers), using BIOVIA Draw (Dassault Systems BIOVIA). The 2D structures were converted into 3D structures using PyRx's Open Babel module by using 500 steps of a steepest descent geometry optimization with the MMFF94 forcefield. The lowest energy conformer generation does not alter the stereochemistry of the input structures. Molecular docking was achieved with the PyRx v0.8 virtual screening software (The Scripps Research Institute, La Jolla, CA, USA) using Vina's encoded scoring function [29]. This is a custom scoring function which combines, as their developers describe, empirical information from both the conformational preferences of the receptor-ligand complexes and experimental affinity measurements [29]. The docking software was set to generate/dock 10 conformers of each input molecular structure. The docking protocol was validated by re-docking the native ligands into their original protein binding sites. The root means square deviation (RMSD) between the predicted and experimental docking pose of the native ligand was calculated. Molecular docking was performed only for cases with aforementioned RMSD values not exceeding a 2 A threshold. The docking grid box coordinates and size were selected to best fit the active binding site (Table 1). Docking scores were recorded as \(\Delta\)G binding energy values (kcal/mol). Protein-ligand binding interactions were analysed using Accelrys Discovery Studio 4.1 (Dassault Systems BIOVIA, San Diego, CA, USA). \begin{table}
\begin{tabular}{c c c c c c} \hline
**Protein** & **PDB ID/** & **Grid Box Center** & **Grid Box Size** & **Naive Ligand** & **References** \\
**Protein** & **Protein Structure** & **Coordinates** & & & N-{[sloucucrly]+r’[adenosylyl]-daiminoostrone} \\
**LARS** & 1 JZQ & \begin{tabular}{c} center,\(x=-27.683\) \\ center,\(x=7.940\) \\ center,\(x=-28.726\) \\ \end{tabular}  & \begin{tabular}{c} size,\(x=15.314\) \\ size,\(y=10.229\) \\ size,\(x=10.025\) \\ \end{tabular}  & \begin{tabular}{c} size,\(x=15.314\) \\ size,\(y=10.229\) \\ \end{tabular}  & \begin{tabular}{c} size,\(y=10.229\) \\ size,\(y=10.025\) \\ \end{tabular}  & \ \begin{tabular}{c} size,\(y=10.029\) \\ size,\(y=10.025\) \\ \end{tabular}  &
\begin{tabular}{c} size,\(y=10. \begin{tabular}{c c c c c c} \multicolumn{6}{c}{Table 1. Cost.} \\ \hline
**Protein** & \ \begin{tabular}{c} **PDB ID/** \\ **Protein Structure** \\ **Resolution** \\ \end{tabular}  & \begin{tabular}{c} **Grid Box Center** \\ **Conordinates** \\ \end{tabular}  & **Grid Box Size** & **Native Ligand** & **References** \\ \hline
**NADPH-oxidase** & 2 CDU & \begin{tabular}{c} center\_x = 18.043 \\ 1.80 A \\ \end{tabular}  & \begin{tabular}{c} size\_x = 13.845 \\ center\_y = \(-\)6.944 \\ center\_z = 0.261 \\ \end{tabular}  & \ \begin{tabular}{c} size\_y = 13.580 \\ size\_y = 19.019 \\ \end{tabular}  & \begin{tabular}{c} \(\Delta\)DP \\ \(\Delta\) \\ \(\Delta\) \\ \end{tabular}  \\ \hline
**DDI1** & 2280 & \ \begin{tabular}{c} center\_x = 34.136 \\ center\_y = 4.049 \\ center\_z = 25.365 \\ \end{tabular}  &
\begin{tabular}{c} size\_x = 8.