Finally, while the accuracy of the chosen docking methodology is not a focus of this paper we do note some encouraging signs for the HTVS scoring function in Glide. For example, all the top scoring molecules for CM (Figure ) are dianions just like the known binder TSA (Figure ) and the CM substrate chorismate. Only 327 out of the 250,000 molecules in the ZINC subset that the initial population is randomly drawn from are dianions so the dianion motif is most likely generated by the GA. Similarly, for the fluorene moiety seen in both carazolol and Figure as well as two ethylene linked aromatic moieties seen in ponatinib and Figures and, but with only 242 and 40 occurrences in the 250K ZINC subset, respectively. For BCD there is a clear preference for both lipophilic (adamantane-like in Figure ) moieties favoring binding to the pocket as well as hydrophilic moieties which are also representative of the structures that bind favorably according to experiments.