title: Chemokine receptor modeling: an interdisciplinary approach to drug design.
abstract: Chemokines and their receptors are integral components of the immune response, regulating lymphocyte development, homing and trafficking, and playing a key role in the pathophysiology of many diseases. Chemokine receptors have, therefore, become the target for both small-molecule, peptide and antibody therapeutics. Chemokine receptors belong to the family of seven transmembrane receptor class A G protein-coupled receptors. The publication of the crystal structure of the archetypal class A seven transmembrane receptor protein rhodopsin, and other G protein-coupled receptors, including C-X-C chemokine receptor 4 and C-C chemokine receptor 5, provided the opportunity to create homology models of chemokine receptors. In this review, we describe an interdisciplinary approach to chemokine receptor modeling and the utility of this approach for structure-based drug design of chemokine receptor inhibitors.
authors.affiliation: Sanofi-Genzyme R&D Center, 49 New York Avenue, Framingham, MA 01701 USA. simon.fricker@genzyme.com.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Fricker
authors.forename: Markus
authors.initials: M
authors.lastname: Metz
mesh_terms: D001665:Binding Sites; D018925:Chemokines / Q000378:metabolism; D015195:Drug Design; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D023581:HIV Fusion Inhibitors; D019707:Receptors, Chemokine