Pharmacophore

A pharmacophore was first defined by Paul Ehrlich in 1909 as "a molecular framework that carries (phoros) the essential features responsible for a drug’s (=pharmacon's) biological activity" (Ehrlich. Dtsch. Chem. Ges. 1909, 42: p.17). In 1977, this definition was updated by Peter Gund to "a set of structural features in a molecule that is recognized at a receptor site and is responsible for that molecule's biological activity" (Gund. Prog. Mol. Subcell. Biol. 1977, 5: pp 117–143). The IUPAC definition of a pharmacophore is "an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response".

In modern computational chemistry, pharmacophores are used to define the essential features of one or more molecules with the same biological activity. A database of diverse chemical compounds can then be searched for more molecules which share the same features located a similar distance apart from each other.

Typical pharmacophore features are for where a molecule is hydrophobic, aromatic, a hydrogen bond acceptor, a hydrogen bond donor, a cation, or an anion. The features need to match different chemical groups with similar properties, in order to identify novel ligands. Ligands receptor interactions are typically “polar positive”, “polar negative” or “hydrophobic”. A well-defined pharmacophore model includes both hydrophobic volumes and hydrogen bond vectors.