scholarly journals A Simulation Analysis and Screening of Deleterious Non-Synonymous Single Nucleotide Polymorphisms (SNPs) in Human CDKN1A Gene

2017 ◽  
Author(s):  
G. M. Shazzad Hossain Prince ◽  
Trayee Dhar
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Simulation Analysis ◽  
In Silico Analysis ◽  
Normal Function ◽  
Nuclear Antigen ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Single Nucleotide ◽  
Cell Cycle Inhibition ◽  
Proliferating Cell

AbstractCDKN1A also known as p21CIP1 /p21WAF1, a cyclin dependent kinase 1, interacts with proliferating cell nuclear antigen (PCNA) resulting in cell cycle inhibition in human. Non-synonymous single nucleotide polymorphisms (nsSNPs), which reside in the coding region of a gene, might distort the normal function of the corresponding protein. In silico analysis in this study followed many different algorithms. Following the final screening of 118 nsSNPs from dbSNP (NCBI), 12 missense SNPs (R19C (C→T), G23D (A→G), V25G (G→T), V25L (C→G), Q29P (A→C→G), F51L (C→T), E56K (A→G), T57I (C→T), G61R (C→G), G61D (A→G), Y151C (A→G) and R156W (C→G→T) were predicted to have deleterious effect by all the algorithms. Of them, R19C, G23D, F51L, Y151C and R156W occurred at the highly conserved site. G23D, F51L variants also occurred at the CDI domain. Homology structures of the protein predicted decrease of energy in mutant models. GV-GD scores predicted only two variants as neutral (V25L, F51L).

In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment

2018 ◽  
Author(s):  
Md. Arifuzzaman ◽  
Sarmistha Mitra ◽  
Amir Hamza ◽  
Raju Das ◽  
Nurul Absar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Protein Stability ◽  
In Silico Analysis ◽  
Normal Activity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Stability Change ◽  
And Function ◽  
Dbsnp Database

ABSTRACTBackgroundMutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.ObjectiveIn this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.MethodFirstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.ResultsA total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.ConclusionThis is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.

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