To computationally explore alternative ligands to the prokaryotic KcsA 1k4c model, a "generating rather than screening" strategy has been developed. The differences between these two types of strategies could be compared to those between going for submarine fishing or waiting for the fish to pass by (submarine-pursuing rather than wait-fishing). To explore such strategy, DW-BEL co-evolutions generating thousands of fitted-children have been combined with ADV affinity consensus to improve predictions accuracies. Among other achievements, some of the results surprisingly predicted high correlations and similar docking-cavities between the two docking programs despite their different algorithms and software languages (python and java), something that could not be reported so clearly in several previous co-evolution studies with other protein /ligand pairs 48, 58, 46 , 44 , 35 .