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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
DOI: 10.2174/0929867043456287

Predicting Molecular Interactions in silico: I. A Guide to Pharmacophore Identification and its Applications to Drug Design

Author(s): Oranit Dror, Alexandra Shulman-Peleg, Ruth Nussinov and Haim J. Wolfson
Pages 71-90 (20)
A major goal in contemporary drug design is to develop new ligands with high affinity of binding toward a given protein receptor. Pharmacophore, which is the three-dimensional arrangement of essential features that enable a molecule to exert a particular biological effect, is a very useful model for achieving this goal. If the three-dimensional structure of the receptor is known, pharmacophore is a complementary tool to standard techniques, such as docking. However, frequently the structure of the receptor protein is unknown and only a set of ligands together with their measured binding affinities towards the receptor is available. In such a case, a pharmacophore-based strategy is one of the few applicable tools. Here we present a broad, yet concise guide to pharmacophore identification and review a sample of applications for drug design. In particular, we present the framework of the algorithms, classify their modules and point out their advantages and challenges.
pharmacophore mapping, pharmacophore modeling, receptor-based pharmacophore, pharmacophore fingerprints, virtual screening, pharmacophore searching, docking, de-novo design, lead generation, computer-aided drug design
School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.