Structural and dynamic characterization of human Wnt2-Fzd7 complex using computational approaches

  • Hourieh Kalhor
  • Mansour Poorebrahim
  • Hamzeh Rahimi
  • Ali Akbar Shabani
  • Morteza Karimipoor
  • Mohammad Reza Akbari EidgahiEmail author
  • Ladan Teimoori-ToolabiEmail author
Original Paper


Wnt and Frizzled (Fzd) family members play crucial roles in the self-renewal of tumor-initiating cells. Until now, only a few studies have addressed the distinct mechanism of Wnt–Fzd interactions. In this study, we suggest a possible interaction mode of Wnt2 with the Fzd7 cysteine-rich domain (CRD)—both of which are up-regulated in some types of cancer. A combination of homology modeling, molecular docking and molecular dynamics (MD) simulations was carried out to study this ligand–receptor complex in great detail. The results demonstrated the unique dynamic behavior of Wnt2 upon binding to Fzd7. Interestingly, the β-strand content of the C-terminal binding site of Wnt2 was obviously reduced when bound to Fzd7 CRD. Moreover, the N-terminal and C-terminal binding sites of Wnt2 appeared to interact with the C-terminal and N-terminal binding sites of Fzd7, respectively. Calculation of the binding energies uncovered the pivotal role of electrostatic and hydrophobic interactions in the binding of Wnt2 to Fzd7 CRD. In conclusion, this study provides valuable insights into the mechanism of the Wnt2-Fzd7 CRD interaction for application in colorectal cancer prevention programs.

Graphical abstract

Flowchart representation of different steps used in this study.


WNT2 protein FZD7 protein, human Structural homology, protein Molecular docking simulation Molecular dynamics simulations 



Three dimensional


Cluster number


Colorectal cancer


Cysteine-rich domain


C-terminal domain




Discrete optimized potential energy




Homology modeling


Lipoprotein receptor related protein


Lowest energy


mouse frizzled


Molecular dynamics


N-terminal domain


Protein Data Bank


Probability density function


Radius of gyration


Root mean square deviation


Root mean square fluctuations


Solvent accessible surface area


Simple point charge


Transcription cell factor


Wingless Int


Xenopus Wnt



This study was supported by the Semnan University of Medical Sciences (Grant Number: 810) and the Pasteur Institute of Iran (Grant Number: 94/0110/15866).

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

Supplementary material

894_2018_3788_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 30 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hourieh Kalhor
    • 1
    • 2
  • Mansour Poorebrahim
    • 2
  • Hamzeh Rahimi
    • 2
  • Ali Akbar Shabani
    • 1
  • Morteza Karimipoor
    • 2
  • Mohammad Reza Akbari Eidgahi
    • 1
    Email author
  • Ladan Teimoori-Toolabi
    • 2
    Email author
  1. 1.Department and Biotechnology Research CenterSemnan University of Medical SciencesSemnanIran
  2. 2.Molecular Medicine DepartmentPasteur Institute of IranTehranIran

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