C(X)CR in silico: Computer-aided prediction of chemokine receptor-ligand interactions

L Roumen; D J Scholten; P de Kruijf; I J P de Esch; R Leurs; C de Graaf

doi:10.1016/j.ddtec.2012.05.002

C(X)CR in silico: Computer-aided prediction of chemokine receptor-ligand interactions

Drug Discov Today Technol. 2012 Winter;9(4):e281-91. doi: 10.1016/j.ddtec.2012.05.002.

Authors

L Roumen¹, D J Scholten¹, P de Kruijf¹, I J P de Esch¹, R Leurs¹, C de Graaf²

Affiliations

¹ Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
² Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands. Electronic address:c.de.graaf@vu.nl.

PMID: 24990665
DOI: 10.1016/j.ddtec.2012.05.002

Abstract

This review will focus on the construction, refinement, and validation of chemokine receptor models for the purpose of structure-based virtual screening and ligand design. The review will present a comparative analysis of ligand binding pockets in chemokine receptors, including a review of the recently released CXCR4 X-ray structures, and their implication on chemokine receptor (homology) modeling. The recommended protein-ligand modeling procedure as well as the use of experimental anchors to steer the modeling procedure is discussed and an overview of several successful structure-based ligand discovery and design studies is provided. This review shows that receptor models, despite structural inaccuracies, can be efficiently used to find novel ligands for chemokine receptors.: