Structure-based virtual screening concepts

Implementation of Cheminformatics Concepts in Structure-based Virtual Screening... 

In the following subsections we address these three points, outlining concepts of assessing the overall druglikenss of molecules, the concentration of subsets of molecules in focused libraries, and the identification of specific leads through structure-based virtual screening techniques. 

The integration of combinatorial chemistry, structure-based library design and virtual screening [268, 269] also resulted in successful applications [270, 271]. It ultimately should result in broader SAR information about directionality and physicochemical requirements of acceptable building blocks. This concept is based on feasible scaffolds for exploring protein subsites using parallel or combinatorial synthesis. 

The pharmacophore concept has been shown to be of high relevance to virtual screening as a filter in structure-based applications or a stand-alone approach. Input for a pharmacophore can come from different sources a ligand, a ligand series, NMR-derived structure of a related macromolecule, or protein X-ray structure. This information has to be generated, if needed, and productively used for virtual screening. 

This chapter discusses the use of structure-based cheminformatics approaches as a powerful alternative virtual screening methodology that is also complementary to traditional approaches. The concepts discussed in this chapter extend cheminformatics approaches typically reserved for ligand-based computational... 

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