Pharmacophore Modeling in Drug Discovery: Methodology and Current Status

Abstract

A pharmacophore describes the framework of molecular features that are vital for the biological activity of a compound. Pharmacophore models are built by using the structural information about the active ligands or targets. The pharmacophore models developed are used to identify novel compounds that satisfy the pharmacophore requirements and thus expected to be biologically active. Drug discovery process is a challenging task that requires the contribution of multidisciplinary approaches. Pharmacophore modeling has been used in various stages of the drug discovery process. The major application areas are virtual screening, docking, drug target fishing, ligand profiling, and ADMET prediction. There are several pharmacophore modeling programs in use. The user must select the right program for the right purpose carefully. There are new developments in pharmacophore modeling with the involvement of the other computational methods. It has been integrated with molecular dynamics simulations. The latest computational approaches like machine learning have also played an important role in the advances achieved. Moreover, with the rapid advance in computing capacity, data storage, software and algorithms, more advances are anticipated. Pharmacophore modeling has contributed to a faster, cheaper, and more effective drug discovery process. With the integration of pharmacophore modeling with the other computational methods and advances in the latest algorithms, programs that have better perfomance are emerging. Thus, improvements in the quality of the pharmacophore models generated have been achieved with these new developments.