Molecular dynamics simulations on SDF-1α: Binding with CXCR4 receptor

Xiaoqin Huang, Jianhua Shen, Meng Cui, Lingling Shen, Xiaomin Luo, Kun Ling, Gang Pei, Hualiang Jiang, Kaixian Chen

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Insights into the interacting mode of CXCR4 with SDF-1α are crucial in understanding the structural and functional characteristics of CXCR4 receptor. In this paper a computational pipeline, integrating protein structure prediction, molecular dynamics simulations, automated molecular docking, and Brownian dynamics simulations were employed to investigate the dynamic and energetic aspects of CXCR4 associating with SDF-1α. The entire simulation revealed the surface distribution feature of electrostatic potentials and conformational "open-close" process of the receptor. The possible binding conformation of CXCR4 was identified, and the CXCR4-SDF-1α binding complex was generated. Arg188-Glu277 salt bridge plays an important role for both the extracellular domain conformational change and SDF-1α binding. Two binding sites were mapped at the extracellular domain (Site 1) and inside the transmembrane domain (Site 2), which are composed of conserved residues. Sites 1 and 2 contribute ∼60% and 40% to the binding affinity with SDF-1α, respectively. The binding model is in agreement with most of the experimental data. Transmembrane VI has more significant motion in the harmonious conformational transition of CXCR4 during SDF-1α binding, which may be possibly associated with signal transduction. Based on the modeling and simulation, a binding mechanism hypothesis between CXCR4 and SDF-1α and its relationship to the signal transduction has been proposed.

Original languageEnglish (US)
Pages (from-to)171-184
Number of pages14
JournalBiophysical Journal
Volume84
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Biophysics

Fingerprint Dive into the research topics of 'Molecular dynamics simulations on SDF-1α: Binding with CXCR4 receptor'. Together they form a unique fingerprint.

  • Cite this

    Huang, X., Shen, J., Cui, M., Shen, L., Luo, X., Ling, K., Pei, G., Jiang, H., & Chen, K. (2003). Molecular dynamics simulations on SDF-1α: Binding with CXCR4 receptor. Biophysical Journal, 84(1), 171-184. https://doi.org/10.1016/S0006-3495(03)74840-1