Predicting molecular interactions in silico: I. A guide to pharmacophore identification and its applications to drug design

Curr Med Chem. 2004 Jan;11(1):71-90. doi: 10.2174/0929867043456287.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Algorithms
  • Computer-Aided Design*
  • Databases, Factual
  • Drug Design*
  • Drug Interactions*
  • Ligands
  • Molecular Conformation
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Receptors, Drug / chemistry

Substances

  • Ligands
  • Receptors, Drug