In de novo evolution, TCM compounds were placed into the H1 and N1 protein binding sites described previously, and Ludifragments were attached to the native structure. The new derivatives were generated in full evolution mode. Derivatives from de novo evolution were subjected to additional screening through Lipinski's rule [106] to rule out orally unstable or pharmacologically inapplicable compounds. As de novo products generated for H1 and N1 proteins differed, all de novo products were re-docked to H1 and N1 proteins to assess binding affinity. De novo products that docked into both H1 and N1 proteins were selected and ranked by the sum of their respective H1 and N1 DockScore. The top ten compounds with the highest DockScore were selected for further structure-based analysis.