Computational Identification and Structural Analysis of Deleterious Functional SNPS in CHN1 Gene Causing Duane Retraction Syndrome

摘要

Here we have evaluated the Single Nucleotide Polymorphisms (SNPs) that can alter the expression and the function in CHN1 gene through computational methods. To explore possible relationships between genetic mutations and phenotypic variation, different computational methods like Sorting Intolerant from Tolerant (SIFT, an evolutionary-based approach), Polymorphism Phenotyping (PolyPhen, a structure-based approach) and I-Mutant 3.0 (support vector machine based tool) are discussed. There were 7 missense mutations; in this we observed 5 variants that were deleterious and damaging respectively. We got 6 non-synonymous SNPs (nsSNPs) (85.71%) to be deleterious by SIFT, I- Mutant 3.0 and PolyPhen-2. Then cation-π interactions in protein structures are identified and analyzed the roles played by Arg, Lys interactions with π (Phe, Tyr or Trp) residues and their role in the structural stability. Then docking analysis between 1MH1 and the native and mutant modeled structures have done. Subsequently, modeling of these 5 variants was performed to understand the change in their conformation with respect to the native CHN1 by computing their root mean square deviation (RMSD). Those 4 missense mutation were due to loss of stability in their mutant structures of CHN1. This was confirmed by computing their total energies using GROMOS 96 force field and these mutations were cross validated with computational programs.