9. Ligand-Based Molecular Design Using Pseudoreceptors

  1. Gisbert Schneider
  1. Darren Fayne

Published Online: 11 OCT 2013

DOI: 10.1002/9783527677016.ch9

De novo Molecular Design

De novo Molecular Design

How to Cite

Fayne, D. (2013) Ligand-Based Molecular Design Using Pseudoreceptors, in De novo Molecular Design (ed G. Schneider), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527677016.ch9

Editor Information

  1. ETH Zürich, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland

Author Information

  1. Trinity College Dublin, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Dublin 2, Ireland

Publication History

  1. Published Online: 11 OCT 2013
  2. Published Print: 13 NOV 2013

ISBN Information

Print ISBN: 9783527334612

Online ISBN: 9783527677016

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Keywords:

  • pseudoreceptors;
  • SBDD;
  • LBDD;
  • structure–activity relationship;
  • m-QSAR;
  • GPCRs

Summary

Computational techniques have successfully been utilized to guide drug design projects–particularly when the target protein involved in progression of the disease is known. The quality and applicability of the model is completely reliant on the biological and chemical data available. If known active compounds exist, their structural and physicochemical features can be utilized to design potentially active novel compounds–ligand-based drug design (LBDD). Knowledge of the 3D structure of the protein enables probing of the binding site and prediction of novel small molecule protein modulators–structure-based drug design (SBDD). Frequently, the protein structure is unknown, so pseudoreceptor modeling can be utilized to infer the protein binding site structure based on complementarity between it and the known active compounds, thereby bridging the realms of LBDD and SBDD. This chapter provides an overview of the technique, highlighting successful example of the methodology exemplifying the various algorithms available.