These heads-only co-evolutions, predicted 3891 non-toxic fittedchildren with higher affinities than their dga parent (Figure , gray circles vs green circle). However, few non-toxic fitted-children predicted affinities < 100 nM, in contrast to those predicted when using the whole dga molecule as parent (Figure ). Nevertheless, the best top-child number 20900 was chosen as the parent (~250 nM) for the second step of alkyl-only co-evolutions. To perform the alkyl-only co-evolutions, a pseudoligand parent was constructed in PyMol from top-child 20900 by elongating its alkyl-chains downward the homoctamer interface to extend its cavity (Figure , red spheres). Furthermore, DW-BEL molecular weight preference criteria were increased from < 600 to < 900 g/mol. The alkyl-only co-evolutions, predicted 2374 fittedgrandchildren. However, only ~ half of the non-toxic fitted-grandchildren predicted higher affinities than their 20900 parent (Figure , red circles vs blue circle). Furthermore, correlations with their ADV affinity estimations extended for a lower range than those predicted when using the whole dga molecule as parent (Figure ). Nevertheless, the top-grandchild with the most abundant scaffold was number 20346 predicting affinities of ~ 4 nM (Table and Figure , red circles), compared to the ~ 250 nM of its 20900 parent (Figure , blue circle). The 6-ring 4x 20346 top-grandchild scaffold (Figure ) was the most representative scaffold among the non-toxic fitted-grandchildren. Ten top-grandchildren data were listed in Table and 100 top-grand children were supplied as Supporting Materials ( 100top-grandchildren.elongatedcavity.dwar and *.pse).