The KcsA central cavity and its hydrophobic lateral extensions were first targeted by DW-BEL co-evolution with several alkyl-qac of known in vitro inhibitory activities (tetrabutylammonium, tetrahexylammonium, tetraoctylammonium). However, most of the randomly generated fitted-children were eliminated by the DW-BEL toxicity and nasty function algorithms during coevolution and/or eliminated by the macro filter after co-evolution . Since their toxicity risk identifications were mostly due to their central N + atom, substitution of N + by one Carbon atom (qcc alternatives), were attempted which resulted in successful generation of DW-BEL non-toxic alternatives. One qcc symmetric molecule which was a non-toxic star-like molecule containing a central Carbon with 4 arms of 4 Carbons, each linked to a terminal Gly, here called 4x4Gly (C25H48N4O8 formula) (Figure , 2D right image), was optimized by coevolution from parents with different C-chain lengths (data not shown). DW-BEL co-evolution from the 4x4Gly parent predicted 2776 non-toxic fitted-children to the KcsA 1k4c central cavity (Table ). Their affinity predictions were confirmed by exceptional high correlations with those from ADV (Figure ). For instance, the top-child number 7810 predicted ~ 0.1 nM docking affinity (Figure , red open circles), in contrast to ~ 1 µM of its 4x4Gly parent or to the toxic tetraoctylammonium inhibitor (Figure , solid and crossed green circles, respectively). The 6-ring 7810 top-child scaffold (Figure ) was the most representative scaffold among the non-toxic fitted-children. Ten top-children data corresponding to Figure , were listed in Table to visualize some of their properties. Complete data for 100 top-children were also supplied as Supporting Materials (100top-children.centralcavity.dwar and *.pse).