Impact of highly deleterious non-synonymous polymorphisms on GRIN2A protein’s structure and function

Abstract

GRIN2A is a gene that encodes NMDA receptors found in the central nervous system and plays a pivotal role in excitatory synaptic transmission, plasticity and excitotoxicity in the mammalian central nervous system. Changes in this gene have been associated with a spectrum of neurodevelopmental disorders such as epilepsy. Previous studies on GRIN2A suggest that non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein’s structure and function. To gain a better understanding of the impact of potentially deleterious variants of GRIN2A, a range of bioinformatics tools were employed in this study. Out of 1320 nsSNPs retrieved from the NCBI database, initially 16 were predicted as deleterious by 9 tools. Further assessment of their domain association, conservation profile, homology models, interatomic interaction, and Molecular Dynamic Simulation revealed that the variant I463S is likely to be the most deleterious for the structure and function of the protein. Despite the limitations of computational algorithms, our analyses have provided insights that can be a valuable resource for further in vitro and in vivo research on GRIN2A-associated diseases.

In vivo and in silicoexperiment onMitragyna speciosaoffers new insight of antidiabetic potentials

“…Furthermore, the values of molecular dynamics such as Rg, RMSD, RMSF, and SASA have shown fluctuations at different time points at 100ns. Several Molecular dynamics simulation studies have been done previously to investigate the stability of molecules over time [65], [66], [67], [68]. However, these values remained constant throughout time, demonstrating that the compound was firmly bound to the receptor ( Figure 6 ).…”

Computational analysis of the functional and structural impact of the most deleterious missense mutations in the human Protein C

“…It was confirmed that nsSNPs positioned at highly conserved amino acid sites showed more deleterious effects than nsSNPs located at non-conversed positions [ 50 , 51 ]. For this purpose, ConSurf, a web-based tool, was used to estimate the degree of evolution and conservation of human PC residues (using conservation scores) and determine their locations in the protein structure (buried or exposed) [ 52 , 53 ].…”

Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis

“…Nonsynonymous SNPs (nsSNPs) in protein-coding regions, which result in alterations to amino acid sequences and the potential creation of mutated proteins with new structural and functional properties, have garnered significant interest. Deleterious nsSNPs at the genomic and/or proteome levels can induce detrimental functions by destabilizing protein tertiary structures, altering the physicochemical characteristics of proteins, and modifying protein–protein interactions, ultimately posing threats to cellular structural integrity 41 , 42 .…”