Molecular modeling of the effects of glycosylation on the structure and dynamics of human interferon-gamma

  • Elena LilkovaEmail author
  • Peicho Petkov
  • Nevena Ilieva
  • Elena Krachmarova
  • Genoveva Nacheva
  • Leandar Litov
Original Paper
Part of the following topical collections:
  1. 8th conference on Modeling & Design of Molecular Materials (MDMM 2018)


Natural hIFNγ is a glycoprotein with two N-glycosylation sites in each monomer chain, which are independently and differentially glycosylated. Although glycosylation is not necessary for the activity of the cytokine, it was proposed that it protects the cytokine from proteolytic degradation and thus extends its circulatory half-life. Here, we report the development of model structures of glycosylated full-length native hIFNγ homodimers. Our aim is to shed light on the mechanism through which glycosylation preserves the integrity of the cytokine molecule. To this end, we employ molecular dynamics simulations to study the interaction of the carbohydrate chains with the receptor-binding sites in the cytokine and with its flexible highly positively charged C-termini. The glycans interact primarily with the globular part of the protein, but also occasionally form contacts with the solvent-exposed and sensitive to proteases C-terminal tails. We show that the glycans restrict the C-termini wagging motion into the solvent, limit their flexibility and keep them closer to the α-helical globule of hIFNγ, thus possibly protecting them from proteolytic processing.


Human interferon-gamma (hIFNγGlycosylation Molecular dynamics simulations Glycan–protein interactions 



This work was supported in part under the Programme for young scientists’ career development at the Bulgarian Academy of Sciences (DFNP-17-146/2017) and under Grants DN-11/20/2017 and DNTS-Austia-01-2/2013 of the Bulgarian Science Fund.

Computational resources were provided by the HPC Cluster at the Faculty of Physics of Sofia University “St. Kl. Ohridski”.

Supplementary material

894_2019_4013_MOESM1_ESM.pdf (15.3 mb)
(PDF 15.3 MB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Information and Communication Technologies at the Bulgarian Academy of SciencesSofiaBulgaria
  2. 2.Faculty of Physics, Atomic Physics DepartmentSofia University “St. Kliment Ohridski”SofiaBulgaria
  3. 3.Institute of Mathematics and Informatics at the Bulgarian Academy of SciencesSofiaBulgaria
  4. 4.Institute of Molecular Biology “Roumen Tsanev” at the Bulgarian Academy of SciencesSofiaBulgaria

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