Ligand binding to anti-cancer target CD44 investigated by molecular simulations

  • Tin Trung Nguyen
  • Duy Phuoc Tran
  • Pham Dinh Quoc Huy
  • Zung Hoang
  • Paolo Carloni
  • Phuc Van Pham
  • Chuong Nguyen
  • Mai Suan Li
Original Paper


CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.


Breast cancer CD44 F-19848A Hyaluronan Steered molecular dynamics Traditional Chinese medicine 



Breast cancer stem cells




Molecular mechanics Poisson Boltzmann surface area


Van der Waals


Traditional Chinese medicine


Molecular dynamics


Steered molecular dynamics


Side chain


Hydrogen bond



This work was supported by Department of Science and Technology at Ho Chi Minh city, Vietnam. We are grateful to Quan Van Vuong for useful discussions and technical assistance. Allocation of CPU time at the supercomputer center TASK in Gdansk (Poland) is highly appreciated.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

894_2016_3029_MOESM1_ESM.doc (950 kb)
Supplementary information 1 File CD44pp_JMM_SI.pdf contains information about the binding free energy of F-19848A obtained by MM-PBSA method, and related data about the binding properties of CD44 and F-19848A. Comparison of the top ten candidate molecules with potential binding to CD44 (in the PDF) (DOC 950 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institute for Computational Sciences and TechnologyHo Chi Minh CityVietnam
  2. 2.University of TechnologyVietnam National University–Ho Chi Minh CityHo Chi Minh CityVietnam
  3. 3.Institute of PhysicsPolish Academy of SciencesWarsawPoland
  4. 4.Center for Molecular and NanoArchitecture (MANAR)Vietnam National University–Ho Chi Minh CityHo Chi Minh CityVietnam
  5. 5.Computational BiomedicineInstitute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum JuelichJuelichGermany
  6. 6.Stem Cell Research and Application LaboratoryUniversity of Science, Vietnam National UniversityHo Chi Minh CityVietnam
  7. 7.Theoretical Physics Research GroupTon Duc Thang UniversityHo Chi Minh CityVietnam
  8. 8.Faculty of Applied SciencesTon Duc Thang UniversityHo Chi Minh CityVietnam

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