In Silico Study of Pyrin and 14-3-3 Protein Modulation During FMF and PAAND

Familial Mediterranean fever (FMF) is a genetically determined disease transmitted through autosomal recessive inheritance. Recently, a rare but similar disease to FMF, pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND), has been discovered. PAAND is inherited dominantly and is characterized by neutrophilic dermatosis and recurrent fevers. The cause of the disease is point mutations in the MEFV gene. The pyrin protein is a product of this gene and is one of the main factors in the disease's progression. This paper examines the interaction between pyrin and the 14-3-3 protein and screens for modulators affecting their interaction. Regulating this interaction is crucial for understanding the mechanism of FMF development, specifically the disruption of this complexation, which leads to inflammatory responses. The pyrin-14-3-3 interaction is essential for designing potential drugs since weakening this interaction can result in inflammation. This research of in silico experiments identified low molecular weight chemical compounds that have a modulating effect on the tertiary structures of mutant variations of pyrin and 14-3-3 proteins. Studies have identified modulator molecules that interact with the FMF-associated mutant structure of pyrin (M694I) and 14-3-3τ. The chemical compounds that result from this process can be used as modulators and as a potential new basis for the development of therapeutic drugs.