To explore chemical space beyond this point and to demostrate the effectiveness of cut-and-join crossover, we used the natural crossover operator to generate and explore new combinatorial libraries from lists of known binders. We selected four of the five targets used as benchmarking targets in the original REvoLd publication : the enzyme Tyrosyl and the receptors Orexin 1, Muscarinic M1, and Y1. The lists of known actives were taken from . The screened libraries were generated from 292 (Tyrosyl), 234 (Orexin), 447 (Muscarinic), and 801 (Y1) known actives, yielding 481 million, 465 million, 182 million, and 316 million potential new molecules, respectively. 20 independent REvoLd runs were conducted against each target, all tested molecules reported, duplicates between runs removed, and the remaining molecules merged into a single results list per target. The results are presented in figure .