A computational study of the chemokine receptor CXCR1 bound with interleukin-8

摘要

CXCR1 is a G-protein coupled receptor,transducing signals from chemokines,in particular the interleukin-8 (IL8) molecules.This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCR1-IL8 complex.By using CXCR4-vMIP-Ⅱ crystallography structure as the homologous template,CXCR1-IL8 complex structure was constructed,and then refined using all-atom molecular dynamics simulations.Through extensive simulations,CXCR1-IL8 binding poses were investigated in detail.Furthermore,the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences.The results indicate that the receptor N-terminal affects the binding of IL8 significantly.With a shorter N-terminal domain,the binding of IL8 to CXCR1 becomes unstable.The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation.