Predicting Molecular Interactions in silico: I. A Guide to Pharmacophore Identification and its Applications to Drug Design
Abstract: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.
Keywords: computer-aided drug design; de-novo design; docking; lead generation; pharmacophore fingerprints; pharmacophore mapping; pharmacophore modeling; pharmacophore searching; receptor-based pharmacophore; virtual screening
Document Type: Review Article
Affiliations: School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.
Publication date: January 1, 2004
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