Computational analysis for the determination of deleterious nsSNPs in human MTHFR gene

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism and plays a central role in DNA methylation and biosynthesis. MTHFR mutations may alter the cellular folate supply which in turn affects nucleic acid synthesis, DNA methylation and chromosomal damage. The identification of number of SNPs in the human genome growing nowadays and hence, the evaluation of functional & structural consequences of these SNPs is very laborious by means of experimental analysis. Therefore, in the present study, recently developed various computational algorithms have been used which can predict the functional and structural consequences of the SNPs. Various computational tools like SIFT, PolyPhen2, PROVEAN, SNAP2, nsSNPAnalyzer, SNPs&GO, PhD-SNP, PMut, I-Mutant, iPTREE-STAB and MUpro were used to predict most deleterious SNPs. Additionally, ConSurf was used to find amino acids conservation and NCBI conserved domain search tool to find conserved domains in MTHFR. Post translational modification sites were predicted using ModPred. SPARKS-X was used to generate 3D structure of the native and mutant MTHFR protein, ModRefiner for further refinement, Varify3D and RAMPAGE to validate structure. Ligand binding sites were predicted using FTsite, RaptorX binding and COACH. Three SNPs i.e. R157Q, L323P and W500C predicted the most deleterious in all the tools used for functional and stability analysis. Moreover, both residues R157, L323 and W500 were predicted highly conserved, buried and structural residues by ConSurf. Post translational modification sites were also predicted at R157 and W500. The ligand binding sites were predicted at R157, L323 and W500.

Computational and artificial neural network based study of functional SNPs of human LEPR protein associated with reproductive function

“…ModPred was used to predict the post‐translational modification (PTM) sites within LEPR protein. This server consists of rationale regression simulations, skilled discretely with a collection of definite sites for diverse polymorphisms . STRING was used to find the synergy of LEPR protein with other analogous proteins.…”

“…This server consists of rationale regression simulations, skilled discretely with a collection of definite sites for diverse polymorphisms. 49 STRING was used to find the synergy of LEPR protein with other analogous proteins. It is essential to explore the objective of the particular protein interfaces with other corresponding protein at the cellular level.…”

Computational analysis of functional single nucleotide polymorphisms associated with SLC26A4 gene

“…These days, more refined computational methods are bieng created, that help in developing high-throughput, practical path in identification of change in structure, capacity and strength of protein as result of some variation [7,21]. Keeping in view the essentialities, the current study was carried out to identify and predict pathogenic SNPs in SLC26A4 gene, their disease associations and the effect of deleterious nsSNPs in the protein structural behavior.…”

In Silico Analysis of Coding/Noncoding SNPs of Human RETN Gene and Characterization of Their Impact on Resistin Stability and Structure

“…Thus, computational analysis can help to select a limited number of prioritizing deleterious SNPs for genetic disease screening [39]. Among the mutations affecting the protein function, nsSNPs are very frequently occurring in many inherited diseases [40]. Nonsynonymous SNPs were essentially described to inhibit protein activity, DNA-protein, or DNA-miRNA binding.…”