Ligand fitting, combinatorial chemistry

The selection of building blocks is based on information derived from, for example, computational chemistry, where potential virtual ligand molecules are modeled to fit the receptor-protein binding site. Combinatorial chemistry commences with a scaffold or framework to which additional groups are added to improve the binding affinity. Compounds are prepared and later screened using HTS. In this way, many compounds are tested within a short time frame to speed up drug discovery. 

Fig. 4.1 Virtual screening tools can be categorized by the compound data to be screened (compound collection, combinatorial library, chemistry space) and the query type (structure-based, ligand-based, descriptor-based, pharmacophore-based). The output is always a list of compounds together with a score quantifying the fit to the query.

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