Molecular dynamics simulations on SDF-1alpha: binding with CXCR4 receptor

Biophys J. 2003 Jan;84(1):171-84. doi: 10.1016/S0006-3495(03)74840-1.


Insights into the interacting mode of CXCR4 with SDF-1alpha 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-1alpha. 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-1alpha binding complex was generated. Arg188-Glu277 salt bridge plays an important role for both the extracellular domain conformational change and SDF-1alpha 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 approximately 60% and 40% to the binding affinity with SDF-1alpha, 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-1alpha binding, which may be possibly associated with signal transduction. Based on the modeling and simulation, a binding mechanism hypothesis between CXCR4 and SDF-1alpha and its relationship to the signal transduction has been proposed.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Base Sequence
  • Binding Sites
  • Chemokine CXCL12
  • Chemokines, CXC / chemistry*
  • Computer Simulation
  • Cryoglobulins
  • Extracellular Space / chemistry
  • Hydrogen Bonding
  • Kinetics
  • Models, Chemical
  • Models, Molecular*
  • Molecular Conformation
  • Motion
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Receptors, CXCR4 / chemistry*
  • Structure-Activity Relationship
  • Surface Properties


  • Amino Acids
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cryoglobulins
  • Receptors, CXCR4
  • macromolecular insoluble cold globulin