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

• Published in: Journal of biomolecular structure & dynamics Vol. 42; no. 5; pp. 2603 - 2615
• Main Authors: Sahoo, Sthitaprajna, Son, Seungwoo, Lee, Hak-Kyo, Lee, Jun-Yeong, Gosu, Vijayakumar, Shin, Donghyun
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 23.03.2024
• Subjects: AIM2; Carrier Proteins - genetics; conservation; DNA, Viral; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Humans; IFI16; Inflammasomes - genetics; Inflammasomes - metabolism; molecular dynamics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Polymorphism, Single Nucleotide; SIFT; Single nucleotide polymorphism; SIFT; conservation; AIM2; Single nucleotide polymorphism; IFI16; molecular dynamics
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2206907

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