Prediction of Binding Mode between Chemokine Receptor CCR2 and Its Known Antagonists using Ligand Supported Homology Modeling

摘要

Chemokines play a crucial role in the trafficking of leukocytes in the body through the binding to their related receptors. Chemokine Receptor 2 (CCR2) belongs to G-Protein Coupled Receptor (GPCR) family and expressed in monocytes, immature dendritic cells, activated T lymphocytes, basophils, and endothelial and vascular smooth-muscle cells. CCR2 binds several chemokines; CCL2, CCL7, CCL8, and CCL13. CCR2 and its ligand have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, organ transplant rejection, and insulin resistance. Knowledge of the structural basis on CCR2-ligand interaction could help facilitate the design of novel CCR2 antagonists. We modeled and predicted the binding sites of widely known CCR2 antagonists, TAK-779 and Teijin-lead (Fig. 1), using ligand supported homology modeling method.