Computational Modelling of the Full Length hIFN-\(\gamma \) Homodimer

Human interferon gamma (hIFN-\(\gamma \)) is an important signalling molecule, which plays a key role in the formation and modulation of immune response. The controversial conclusions concerning the function of hIFN-\(\gamma \) C-termini as well as the lack of structural information about this domain motivated us to perform molecular dynamics simulations in order to model the structure of the hIFN-\(\gamma \) C-terminal part. The simulations were carried out with the CHARMM22 force field, starting from a fully extended conformation of the C-termini. They showed unambiguously that the C-termini tend to approach the globular part of the protein, so that the whole hIFN-\(\gamma \) molecule adopts a more compact conformation. The energetic favourability of the more compact conformations of the whole cytokine was also confirmed by means of free energy perturbation simulations.