Scoring the Design

Evaluation of candidate compounds is the most critical step in de novo design. It is the duty of the fitness function to decide whether a composed virtual molecule is kept or discarded in deterministic algorithms. One must always be aware that it is the used fitness function that defines the search space for novel molecules. 

Using the TAR RNA ligand acetylpromazine as a template structure, FLUX suggested compound 7.8 as a result of automated fragment-based de novo design. Compound 7.9 was derived from this precursor, synthesized and successfully tested in a binding assay. The distribution of pharmacophoric points is very similar in 7.7 and 7.9. 

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