In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene

Hussain, Muhammad; Shaik, Noor Ahmad; Al‐Aama, Jumana Y.; Asfour, Hani Z.; Khan, Fatima; Masoodi, Tariq; Khan, Muhammad Akhtar; Shaik, Nazia Sultana

doi:10.1016/j.gene.2012.07.014

Cited by 58 publications

(33 citation statements)

References 32 publications

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“…I‐Mutant was classified as one of the most sensitive predictor tool to detect protein stability changes [Khan and Vihinen, ]. Other studies have also demonstrated the utility of various computational tools in predicting the deleterious nature of nucleotide variations to the structure or function of different disease related genes based on sequence and/or structure based pathogenicity prediction methods [Hussain et al, ; Doss and Magesh, ; Mohamoud et al, ].…”

Section: Discussionmentioning

confidence: 99%

A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

Banaganapalli

Mohammed

Khan

et al. 2016

J of Cellular Biochemistry

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Genetic mutations in MED12, a subunit of Mediator complex are seen in a broad spectrum of human diseases. However, the underlying basis of how these pathogenic mutations elicit protein phenotype changes in terms of 3D structure, stability and protein binding sites remains unknown. Therefore, we aimed to investigate the structural and functional impacts of MED12 mutations, using computational methods as an alternate to traditional in vivo and in vitro approaches. The MED12 gene mutations details and their corresponding clinical associations were collected from different databases and by text-mining. Initially, diverse computational approaches were applied to categorize the different classes of mutations based on their deleterious impact to MED12. Then, protein structures for wild and mutant types built by integrative modeling were analyzed for structural divergence, solvent accessibility, stability, and functional interaction deformities. Finally, this study was able to identify that genetic mutations mapped to exon-2 region, highly conserved LCEWAV and Catenin domains induce biochemically severe amino acid changes which alters the protein phenotype as well as the stability of MED12-CYCC interactions. To better understand the deleterious nature of FS-IDs and Indels, this study asserts the utility of computational screening based on their propensity towards non-sense mediated decay. Current study findings may help to narrow down the number of MED12 mutations to be screened for mediator complex dysfunction associated genetic diseases. This study supports computational methods as a primary filter to verify the plausible impact of pathogenic mutations based on the perspective of evolution, expression and phenotype of proteins. J. Cell. Biochem. 117: 2023-2035, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

Banaganapalli

Mohammed

Khan

et al. 2016

J of Cellular Biochemistry

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“…This threshold was fixed at 0.005 or less. SIFT scores were classified as indicating that the SNP would be damaging (0.00–0.05), potentially damaging (0.051–0.10), borderline (0.101–0.20), or tolerable (0.201–1.00) [20].…”

Section: Methodsmentioning

confidence: 99%

An Approach to Identify SNPs in the Gene Encoding Acetyl-CoA Acetyltransferase-2 (ACAT-2) and Their Proposed Role in Metabolic Processes in Pig

et al. 2014

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The novel liver protein acetyl-CoA acetyltransferase-2 (ACAT2) is involved in the beta-oxidation and lipid metabolism. Its comprehensive relative expression, in silico non-synonymous single nucleotide polymorphism (nsSNP) analysis, as well as its annotation in terms of metabolic process with another protein from the same family, namely, acetyl-CoA acyltransferase-2 (ACAA2) was performed in Sus scrofa. This investigation was conducted to understand the most important nsSNPs of ACAT2 in terms of their effects on metabolic activities and protein conformation. The two most deleterious mutations at residues 122 (I to V) and 281 (R to H) were found in ACAT2. Validation of expression of genes in the laboratory also supported the idea of differential expression of ACAT2 and ACAA2 conceived through the in silico analysis. Analysis of the relative expression of ACAT2 and ACAA2 in the liver tissue of Jeju native pig showed that the former expressed significantly higher (P<0.05). Overall, the computational prediction supported by wet laboratory analysis suggests that ACAT2 might contribute more to metabolic processes than ACAA2 in swine. Further associations of SNPs in ACAT2 with production traits might guide efforts to improve growth performance in Jeju native pigs.

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“…Numerous softwares and webservers are available for assessing changes in the properties of mutant sequence and structure of proteins. Impact of mutations on the molecular characteristics of a protein via computational workflow have been implemented previously for cancer (Hussain et al, 2012, Kumar et al, 2013Doss et al, 2014;Ozbabacan et al, 2014;Abdulazeez and Borgio, 2016; M A N U S C R I P T ACCEPTED MANUSCRIPT 5 Basharat and Yasmin, 2016a; Singh and Mistry, 2016), neurodegenerative disorders , Kamaraj et al, 2014Qian et al, 2015), cardiovascular disease (Ramesh et al, 2013), dengue shock syndrome (Taqi et al, 2016), inflammatory disorders (Dabhy andMistry, 2014, Ozbabacan et al, 2014) etc. Computational analysis aids in understanding the molecular mechanism behind pathogenic nsSNPs in correlation to its functional and structural damaging properties.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

Basharat

Messaoudi

Ruba

et al. 2016

Gene

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In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene

Cited by 58 publications

References 32 publications

A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

An Approach to Identify SNPs in the Gene Encoding Acetyl-CoA Acetyltransferase-2 (ACAT-2) and Their Proposed Role in Metabolic Processes in Pig

NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

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