3-D Pharmacophores in drug discovery

In this chapter we review the use of 3-D pharmacophores in drug discovery. Recent advances are highlighted, including the application of pharmacophore descriptors generated both from ligands and protein binding sites. The app lication of 3-D pharmacophore fingerprints as molecular descriptors for sim ilarity and diversity applications such as virtual screening, library desig n and QSAR is discussed. In addition, we highlight the quantification of st ructure-based diversity using site-derived fingerprints, and review virtual screening methods using both single refined hypotheses and the fingerprint s of multiple potential hypotheses. Further, we discuss methods that take p rotein flexibility and molecular shape-into account.