ABSTRACT
A pharmacophore can be defined as a three-dimensional configuration of chemical
features that is necessary for binding or modulating biological activity at a given receptor site (1). Feature-based pharmacophores are useful search queries for mining databases for new leads (2, 3) or predicting activities of proposed structures (4-6). Feature definitions are not limited to descriptions of specific chemical topology. Rather, they describe the kinds of interactions important for ligand-receptor binding. They generally include hydrogen bond acceptors, hydrogen bond donors, and hydrophobes but have also been defined for positive and negative charge centers and extended to other custom definitions (7, 8). This allows for a broad range of topologies to be considered as drug candidates. Substitution of one chemical moiety for another while still maintaining the same overall chemical functionality can be an effective means of circumventing unwanted side effects inherent to a particular class of molecules.
