Pharmacophore Modelling

A pharmacophore is the abstract, three-dimensional arrangement of chemical features — hydrogen-bond donors and acceptors, hydrophobic centres, aromatic ring...

A pharmacophore is the abstract, three-dimensional arrangement of chemical features — hydrogen-bond donors and acceptors, hydrophobic centres, aromatic ring centroids, and positively or negatively ionisable groups — that is necessary and sufficient for a molecule to interact productively with a specific biological target, independent of any particular chemical scaffold that presents that arrangement. Pharmacophore models may be derived directly from a structure-based analysis of a target's binding site (structure-based pharmacophore) or, in the absence of target structural data, from the common three-dimensional features shared by a training set of known active compounds (ligand-based pharmacophore); once established, a pharmacophore model can be used to rapidly screen very large virtual compound databases for molecules capable of presenting the required feature arrangement, offering a computationally efficient complement to full molecular docking, particularly valuable for scaffold-hopping applications in which chemically novel structures satisfying the same essential pharmacophore are specifically sought.