Impact of nsSNPs in human AIM2 and IFI16 gene: a comprehensive in silico analysis

AIM2 and IFI16 are the most studied members of AIM2-like receptors (ALRs) in humans and share a common N-Terminal PYD domain and C-terminal HIN domain. The HIN domain binds to dsDNA in response to the invasion of bacterial and viral DNA, and the PYD domain directs apoptosis-associated speck-like protein via protein-protein interactions. Hence, activation of AIM2 and IFI16 is crucial for protection against pathogenic assaults, and any genetic variation in these inflammasomes can dysregulate the human immune system. In this study, different computational tools were used to identify the most deleterious and disease-causing non-synonymous single nucleotide polymorphisms (nsSNPs) in AIM2 and IFI16 proteins. Molecular dynamic simulation was performed for the top damaging nsSNPs to study single amino acid substitution-induced structural alterations in AIM2 and IFI16. The observed results suggest that the variants G13V, C304R, G266R, and G266D for AIM2, and G13E and C356F are deleterious and affect structural integrity. We hope that the suggested deleterious nsSNPs and structural dynamics of AIM2 and IFI16 variants will guide future research to better understand the function of these variants with large-scale studies and may assist in fresher therapeutics focusing on these polymorphisms.Communicated by Ramaswamy H. Sarma

Automated summary

AIM2 and IFI16, the most studied members of AIM2-like receptors (ALRs) in humans, play crucial roles in protecting against pathogenic assaults. This study identified deleterious and disease-causing genetic variations in AIM2 and IFI16 proteins using computational tools and analyzed their structural alterations through molecular dynamics simulation. The findings suggest that specific variants in AIM2 (G13V, C304R, G266R, and G266D) and IFI16 (G13E and C356F) affect structural integrity. These results provide valuable insights for future research on the function and therapeutic targeting of these polymorphisms.