Abstract: The knowledge of structural organization of proteins is crucial in understanding their role in the cell and the related molecular mechanisms. Comparative modelling has already become one of the most effective computational approaches in facilitating structural/functional characterization of many protein-coding sequences across genomes and it is based on the assumption that homologous proteins adopt the same fold to have the same function. On this basis, it is possible to model the 3D structure of a protein if it is known at least one experimental model of an homologous protein. However, it is evident that a large number of proteins, probably all, may assume different conformations depending on the different environmental conditions or the interaction with other molecules. Conformational modifications occur when a protein changes its monomeric / oligomeric state, enzymes adapt their conformation to the substrate when it is recognized, but also, very different secondary structures are observed in the normal and pathological forms of the prion protein. We are interested to apply the comparative modelling to predict the different conformations assumed by a protein to exert its biological activities or in different environmental conditions. In this work we applied the comparative modelling methods to create models of the interleukin 1beta (IL-1beta) and to investigate the conformational changes occuring when this protein interacts with its receptor (IL-1R).