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

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. School of Chemical Sciences, Universiti Sains Malaysia, 11800, USM, Pulau Pinang, Malaysia

    Erma Fatiha Muhammad & Rohana Adnan

  2. Department of Chemistry, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor Darul Ehsan, Malaysia

    Muhammad Alif Mohammad Latif & Mohd Basyaruddin Abdul Rahman

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  1. Erma Fatiha Muhammad
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Correspondence to Rohana Adnan.

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Muhammad, E.F., Adnan, R., Latif, M.A.M. et al. Theoretical investigation on insulin dimer-β-cyclodextrin interactions using docking and molecular dynamics simulation. J Incl Phenom Macrocycl Chem 84, 1–10 (2016). https://doi.org/10.1007/s10847-015-0576-x

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