Theoretical Investigation of Binding Mechanism between CXCR3 and Chemokines

Jia-Xian Yin1, Jen-Shiang K. Yu*,1,2

1Institute of Bioinformatics and Systems Biology, and 2Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University

The C-X-C Motif Chemokine Receptor (CXCR3) is activated by multiple chemokines and induces downstream pathways. CXCR3 is associated with some diseases, the sequence similarity between each chemokine is low, which implies the possibility of CXCR3 capturing different chemokines with different mechanisms, and the post-translational-modification tyrosine sulfations on CXCR3 were reported to be necessary for the binding of chemokine.2 However, the structure of CXCR3 and its binding mechanisms are still unclear. In this study, CXCR3 and a chemokine called CXCL4L13 are selected to investigate the binding mechanisms. Homology modeling, molecular dynamics (MD) simulation, and protein-protein docking are combined to study the binding mechanisms. We have constructed a strategy to build a CXCR3-chemokine complex, and perform preliminary analyses of MD trajectories including binding energies, and protein-protein interactions and conformational changes. The binding mechanisms are being investigated in detail.