Thousands of unique children were randomly generated by the co-evolution algorithms provided by DataWarrior-Build Evolutionary Library (DWBEL). DWBEL-conformers were selected to computationally target the gpGVHSV R4-TrD interface. To initiate DWBEL, the selection of an appropriated 2D molecule as initial parent proved to be not trivial. After preliminary dockings to manually designed hypothetical ligands, the highest affinities to the R4-TrD interface inner cavity were predicted by those molecules with 3-fold star-shaped conformers simultaneously docking to gpGVHSV amino acids located at their 3 chains rather than only at 1 or 2 chains. Alternative 3-fold star-shaped 2D molecules were manually designed with different central atoms / rings and arm sizes between 1-6 carbons. The conformer number 30 (cn30) (Figure ), was chosen as parent (Supporting Materials / StarShapedLigands.dwar) and the gpGVHSV-cn30 R4-TrD as target cavity for DWBEL.