Theoretical investigation on insulin dimer-β-cyclodextrin interactions using docking and molecular dynamics simulation

  • Erma Fatiha Muhammad
  • Rohana Adnan
  • Muhammad Alif Mohammad Latif
  • Mohd Basyaruddin Abdul Rahman
Original Article


In our study, molecular docking and molecular dynamics (MD) simulations were performed in order to explore the interactions between human insulin and β-cyclodextrin (β-CD). Molecular docking study was performed using the Autodock v4.2 program to determine the number of β-CD molecules that adhere to the binding sites of insulin. A random structure docking approach using an initial ratio of 1:1 insulin-β-CD was conducted and from these, additional β-CDs were added. Molecular docking results revealed that a maximum of four β-CDs are able to bind to the insulin structure with the 1:3 insulin-β-CD ratio producing the lowest binding free energy. The docked conformations showed that hydrophobic interactions played a crucial role in insulin-β-CD conformational stability in addition to the formation of hydrogen bonds. A 50 ns MD simulation was further conducted using an NPT ensemble to verify the results obtained by molecular docking. The analysis of the MD simulation results of the 1:3 insulin-β-CD formation system conclude that a good interaction exists between insulin and β-CDs and the RMSD value obtained was 4.00 ± 0.50 Å. The RMSF profiles of insulin in the 1:3 insulin-β-CD formation also show reduced amino acid residues flexibility as compared to the free insulin system. The theoretical results indicated the presence of significant interactions between insulin and β-CD which could provide interesting insights into an insulin formulation.


Insulin β-Cyclodextrin Molecular docking Molecular dynamics simulation 



The study was financially supported by the funding from Universiti Sains Malaysia through the Research University Grant (Grant No. 1001/PKIMIA/815099). The authors gratefully acknowledge the technical assistance from the staff of the Department of Chemistry, Faculty of Science, Universiti Putra Malaysia.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Erma Fatiha Muhammad
    • 1
  • Rohana Adnan
    • 1
  • Muhammad Alif Mohammad Latif
    • 2
  • Mohd Basyaruddin Abdul Rahman
    • 2
  1. 1.School of Chemical SciencesUniversiti Sains MalaysiaUSMMalaysia
  2. 2.Department of ChemistryUniversiti Putra MalaysiaUPM SerdangMalaysia

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