Pharmacophore Mapping and Virtual Screening

Abstract

3D pharmacophore-based techniques have become one of the most important approaches for the fast and accurate virtual screening of databases with millions of compounds. The success of 3D pharmacophores is largely based on their intuitive interpretation and creation, but the virtual screening with such three-dimensional geometric models still poses a considerable algorithmic and conceptual challenge. Most current implementations favor fast screening speed at the detriment of accuracy. This review describes the general strategies and algorithms employed for 3D pharmacophore searching by some current pharmacophore modeling platforms and will highlight their differences. Developing new medical drugs is expensive. Among the first steps is a screening process, in which molecules in existing chemical libraries are tested for activity against a given target. This requires a lot of resources and manpower. Therefore it has become common to perform a virtual screening, where computers are used for predicting the activity of very large libraries of molecules, to identify the most promising leads for further laboratory experiments. Since computer simulations generally require fewer resources than physical experimentation this can lower the cost of medical and biological research significantly. In this paper we review practically fast algorithms for screening databases of molecules in order to find molecules that are sufficiently similar to a query molecule.