Advances in Pharmacophore Modeling and Its Role in Drug Designing

Abstract

Pharmacophore modeling is a central method in the ligand-based drug designing module. Its basis lies in developing a scaffold or an empirical molecule based on a group of known inhibitors to a target. The empirical molecule will contain features that are common to the known inhibitors and specified as donors, acceptors, rings, positively charged, or negatively charged. These five features or a combination of some of these features at specific distances make a pharmacophore. This pharmacophore facilitates the identification of other novel compounds that are specific and sensitive as well as effective inhibitors to a receptor. This method is particularly effective when the structural annotations are unavailable for the target. Thus pharmacophore modeling is a tool in drug discovery where screening of the pharmacophore built leads to the discovery of novel compounds against the target. Using these techniques as well as variations of these techniques, millions of compounds can be screened in a matter of hours to shortlist actives. Variations might be based on building a pharmacophore by the energy contribution of features in a single molecule against a specific target. Otherwise, based on only the geometric features of the active site in a target, a pharmacophore can be designed. Thus a designed pharmacophore can be used to screen novel agonists and antagonists that are specific to targets, to screen toxicants, to identify unknown targets, and to screen out best molecular docking results.