期刊
COMPUTATIONAL BIOLOGY AND CHEMISTRY
卷 74, 期 -, 页码 20-30出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.compbiolchem.2018.02.022
关键词
In silico analysis; Human MTHFR gene polymorphism; Single nucleotide polymorphisms; Folate metabolism; Deleterious prediction
资金
- INSPIRE division of Department of Science and Technology (DST, New Delhi)
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, Varify 3D 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. (C) 2018 Elsevier Ltd. All rights reserved.
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