As researchers continue to search for new targets of therapeutic interest, transmembrane and G-protein coupled receptors are of ever-increasing importance. However, crystal structures for these targets may be impossible to resolve, posing great challenges in rational drug design. Structure-based virtual screening is not an option when the active site geometry is unknown, but assaying an entire library for hits is an inefficient and expensive proposition.
Pharmacophore modeling solves this problem by determining the spatial arrangement of chemical features that confer drug activity toward a target receptor. Having established the chemical space occupied by active ligands, pharmacophore modeling software allows researchers to create 3D structure-activity relationships, screen databases, and generate hits without the benefit of a receptor structure.