Co-evolution proceeded according to user-defined criteria consisting in both preferences and relative 1-4 weights. The criteria were, minimal DW docking-scores with relative weight 4 (to maximize docking affinities using the optimal force-field mmff94s + algorithm 37 ), molecular weight <= 600 g/mol with relative weight 2 and cLog <=8 with relative weight 1 (to limit children unspecificities) and Toxicity risk <=1 with relative weight 4 (to reduce hundreds of toxicity risks and/or nasty functions during co-evolution). Because computer memory limitations, the maximal number of consecutive runs were limited to 3, but after 24 hours or when reaching RAM >100 Gb, runs were manually stopped. The resulting DW output docking-scores of the fitted-children were expressed in negative unitless values (the more negative, the higher affinity).