In Silico Analysis of the Interaction of Human Interferon γ C-terminal Peptide and Heparan Sulphate Derived Octasaccharides

Human interferon γ (hIFNγ) is a crucial immunomodulatory cytokine that exerts its effects by binding to a high-affinity receptor complex on the cell surface. In addition to receptor binding, hIFNγ also displays strong affinity for heparin and heparan sulphate, primarily via its C-terminal domain. This interaction influences various physicochemical properties of the cytokine, including its receptor affinity, and could be harnessed for designing hIFNγ inhibitors. Current experimental methods cannot precisely determine sulphate group arrangements in heparin-like and HS-like octasaccharides, which influence charge distribution and potentially affect their binding affinity to the hIFNγ C-terminal peptide. Here, we propose an in silico approach to explore different sulphation patterns in octasaccharides containing one acetyl and seven sulphate groups, aiming to identify those that optimize binding to the hIFNγ C-terminal peptide.