Chemical cherry-picking

The term hit confirmation, as we define it, involves three components reproducibility, confirmation of chemical structure, and confirmation of chemical purity. Confirmation of hit reproducibility requires that the subset of library compounds designated as hits in the primary screen be identified, that samples of each of these be obtained from the library bank (a process often referred to as cherry picking ), and that these samples be retested, at least once but preferably multiple times, to determine if they reproducibly confer an inhibition percentage of the target enzyme... 

Fig. 15.24 RADDAR a nearly infinite number of chemical structures can be generated by computationally enumerating combinatorial library proposals. Cherry picking of interesting candidates (proposed structures) based on defined computational algorithms allows the chemist to synthesize the relevant subsets of theoretically accessible molecules.

Although most applications were of the cherry-picking type design, the combinatorial design of new chemical libraries should also be feasible. In this case, the scores obtained with the various models can be used to sort the virtual library, followed by building block frequency analysis cf. Focus2D) to determine which reagents should be used in chemical synthesis. Alternatively, combinatorial optimization approaches, such as those in described in ref. 4, can be applied where the model-predicted scores are used as the objective function for optimization. 

---