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

57 Citations (Scopus)

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
StatePublished - Jan 1 2003
Externally publishedYes

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CXCR4 Receptors
Molecular Dynamics Simulation
Signal Transduction
Static Electricity
Salts
Binding Sites
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Huang, X., Shen, J., Cui, M., Shen, L., Luo, X., Ling, K., ... Chen, K. (2003). Molecular dynamics simulations on SDF-1α: Binding with CXCR4 receptor. Biophysical Journal, 84(1), 171-184.

Molecular dynamics simulations on SDF-1α : Binding with CXCR4 receptor. / Huang, Xiaoqin; Shen, Jianhua; Cui, Meng; Shen, Lingling; Luo, Xiaomin; Ling, Kun; Pei, Gang; Jiang, Hualiang; Chen, Kaixian.

In: Biophysical Journal, Vol. 84, No. 1, 01.01.2003, p. 171-184.

Research output: Contribution to journalArticle

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, vol. 84, no. 1, pp. 171-184.
Huang X, Shen J, Cui M, Shen L, Luo X, Ling K et al. Molecular dynamics simulations on SDF-1α: Binding with CXCR4 receptor. Biophysical Journal. 2003 Jan 1;84(1):171-184.
Huang, Xiaoqin ; Shen, Jianhua ; Cui, Meng ; Shen, Lingling ; Luo, Xiaomin ; Ling, Kun ; Pei, Gang ; Jiang, Hualiang ; Chen, Kaixian. / Molecular dynamics simulations on SDF-1α : Binding with CXCR4 receptor. In: Biophysical Journal. 2003 ; Vol. 84, No. 1. pp. 171-184.
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