In Silico Single Nucleotide Polymorphism Analysis in Human Glutamate Dehydrogenase

Abstract

In the present study, various in silico analysis tools were used to analyze the structural and functional effect of non-synonymous or amino acid-changing single nucleotide polymorphisms (nsSNPs) in the human glutamate dehydrogenase (GDH) protein associated with HI/HA syndrome. Total 16 nsSNPs data were collected from various published literatures and analyzed to identify high-risk nsSNPs by evolutionary conservation analysis using ConSurf server. I-Mutant tool was used to examine whether these high-risk nsSNPs alter the structural stability of GDH protein. The results of I-Mutant revealed that each high-risk nsSNPs decreases the stability except N410 and S445 of GDH protein. In addition, ConSurf identified a number of other conserved residues and short patterns that may be structurally and functionally relevant. A 37 amino acid long conserved motif from 370 to 406 was also identified which contains 15 highly conserved and buried residues and 7 highly conserved and exposed residues. This study is very extensive in silico analysis of HI/HA syndrome associated mutations in the human GDH protein and will be a valuable contribution for the better understanding the effect of nsSNPs on structural stability of the human GDH.