Such above mentioned co-evolutions generated tens of thousands of raw-children with random small molecular changes. After numbered by their generation ID, the conformers that best-fitted the gpGVHSV-cn30 cavity, molecular weight, hydrophobicity and non-toxicity-risk criteria, were retained for each generation. Consecutive generations of non-toxic best-fitted DWBEL-conformers were repeated during 2-4 consecutive runs of ~ 100 generations per run. Each run re-started co-evolution from cn30 avoiding raw-children duplicates. The affinities predicted by non-toxic best-fitting R4-TrD DWBEL-conformers (Figure , blue circles) were finally compared to affinities predicted by ADV-conformers. The ADV blind-docking was employed to identify those conformers which not only predicted higher affinities (Figure , red circles) but also conserve their R4-TrD crosstargeting DWBEL-conformers. The cn30 and gpGVHSV-cn30 co-evolution for 2-4 consecutive runs predicted some correlation trend between non-toxic fitted-children DWBELconformers and their corresponding ADV-conformers (Figure , red open and solid circles). Additionally, most of the conformers predicted improvements in their DWBEL or ADV affinities compared to their initial cn30 parent. Also, the children generated by 4 runs predicted higher affinities (lower docking-scores) than those predicted by 2 runs (Figure To compare the cavity preferences of the ADV-conformers, the approximated percentage distribution of their targets were calculated among three pre-defined gpGVHSV cavities. Results showed that those top ADV-conformers predicting the highest docking affinities (~ 0.2-100 nM) (Figure , gray rectangle and 2B, red solid circles) targeted R4-TrD at the center of the trimer inner cavity cross-docking their 3 chains (33-37 %, n=834-3313 non-toxic fitted-children ADVconformers, respectively) (Figure , red up arrow). However, two additional docking cavities were also preferred by alternative ADV-conformers. Thus, some children that targeted R4-TrD by DWBEL-conformers, also targeted Bc by different ADV-conformers (Figure , red down arrow). The wider grid of ADV compared to DWBEL, may explain such differences. About, 60-58 % of children ADVconformers preferred Bc at the bottom of TrD α-helices, although with > 10-fold lower affinities than those children which cross-docked 3 chains at the R4-TrD interface (Figure ). Additionally, an smaller percentage of ADV-conformers, preferred targeting to the sides (Sc) of the homotrimer (5-2 %) (Figure , red left arrow).