Background: Familial Mediterranean Fever (FMF) is a prototypical hereditary
autoinflammatory disease affecting principally Mediterranean populations and characterized by
recurrent frequent fever and inflammation. The disease is essentially caused by inherited mutations in
the MEFV gene which encodes pyrin protein. The reported mutations are mostly located on the B30.2
domain in the C-terminal end of the protein.
Objective: The present study reports a structural comparison of the five most common mutated
structures including M694V, V726A, M694I, R761H, and M680I. The aim of this study was to
determine the structural and functional disorders caused by the mutations in the human pyrin protein.
Results: The comparison revealed that all mutations make overall changes in the structure of the
domain. Further, the effects of these mutations on structural and molecular behavior of the B30.2
domain were compared with the native structure using MD simulation by GROMACS software. The
results revealed that all the studied mutants have a destabilizing effect on the protein structure.
Additionally, analyzing the projection of the motions of the proteins in phase space demonstrates high
rigidity of the mutated structures in comparison with the native protein.
Conclusion: The results of simulations elucidate how the mutations affect the physiological
functioning of the pyrin B30.2 domain and cause the occurrence of the FMF disease.