3D Pharmacophore Modeling Techniques in Computer‐Aided Molecular Design Using LigandScout

This chapter reviews theory related to pharmacophore models and guide the user through six essential workflows using LigandScout: structure-based pharmacophore modeling, ligand-based pharmacophore modeling, creating shared-feature pharmacophore models, accurate virtual screening and pharmacophore editing in the active site, Hit analysis and parallel virtual screening. It includes some tutorials involving the creation of 3D-chemical feature pharmacophore models and the use of these models to find biologically active molecules using virtual screening methods. Pharmacophore modeling together with virtual screening have become increasingly popular in the last decades and matured to a valuable and efficient basis for a wide variety of computer-aided drug design projects. The most common representation of pharmacophores is a spatial arrangement of so-called chemical (or pharmacophoric) features that describe essential structural elements and/or observed ligand-receptor interactions by means of geometric entities. The chapter provides an overview of the methodological details and applicability of the most commonly used approaches for creating pharmacophore models.