The DataWarrior-Build Evolutionary Library (DW-BEL) algorithms were employed to generate tens of thousands of raw unique children from one parent molecule and select those fitting an initial protein-ligand cavity (fittedchildren). The Java's DW program was updated for Windows as described before (Table ) including some modifications to adapt to large number of runs. The initial parent molecules were selected from previously proposed KcsA ligands such as quaternary-ammonium compounds (qac) , diacyl-glycerol (dga) or user-designed pseudoligands. Fine-tuning of possible alternatives were introduced by optimizing less-toxic derivatives (i.e., substituting the central N + by C in qac compounds), restricting parts of the initial parent molecules with the DW-BEL lazo option (i.e., head of lipids or hydrophobic alkyl chains) or introducing pseudoligands by PyMol elongation of alkyl-chains.