摘要
CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-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.
CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-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.
作者
王洋
Cecylia Severin Lupala
王亭
李选选
Ji-Hye Yun
Jae-hyun Park
金泽宇
Weontae Lee
汤雷翰
刘海广
Yang Wang, Cecylia Severin Lupala1, Ting Wang, Xuanxuan Li, Ji-Hye Yun, Jae-hyun Park4, Zeyu Jin, Weontae Lee, Leihan Tan, and Haiguang Liu(1 Complex Systems Division, Beijing Computational Science Research Center, Beijing 100193, China 2 Genome Center, University of California, Davis, 451 East Health Science Drive, Davis, CA, 95616, USA 3 Department of Engineering physics, Tsinghua University, Beijing 100086, China 4Department of Biochemistry, College of Life Science ＆ Biotechnology, Yonsei University, Seou103722, South Korea 5 Department of Physics and Institute of Computational and Theoretical Studies, Hong Kong Baptist University, Hong Kong, Chin)
基金
Project supported by the National Natural Science Foundation of China(Grant Nos.11575021,U1530401,and U1430237)
the National Research Foundation of Korea(Grant Nos.NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213)
