scholarly journals In-Silico Methods for Investigating the Effect of Single Nucleotide Polymorphisms on the Structure and Function of Proteins: A Review

2019 ◽  
Author(s):  
Ebenezer Asiedu
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
In Silico ◽  
Drug Response ◽  
Fast Track ◽  
Structure And Function ◽  
Nucleotide Polymorphisms ◽  
Laboratory Studies ◽  
Single Nucleotide ◽  
And Function ◽  
In Silico Methods

Single nucleotide polymorphisms (SNP) are associated with diseases and drug response variabilities in humans. Elucidating the damaging and disease-associated SNPs using wet-laboratory approaches can be challenging and resource-demanding due to the large number of SNPs in the human genome. Due to the growth in the field of computational biology and bioinformatics, algorithms have been developed to help screen and filter out the most deleterious SNPs that are worth considering for wet-laboratory studies. Here we review the existing in-silico based methods used to predict and characterize the effects of SNPs on protein structure and function. This cutting-edge approach will facilitate the search for novel therapeutics, help understand the etiology of diseases and fast-track the personalized medicine agenda.

scholarly journals Comprehensive Characterization of the Coding and Non-coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools.

2021 ◽  
Author(s):  
Shamima Akter ◽  
Shafaat Hossain ◽  
Md. Ismail Hosen ◽  
Hossain Uddin Shekhar
Keyword(s):  
Hydrogen Bonds ◽  
Single Nucleotide Polymorphisms ◽  
Genome Wide Association Study ◽  
Urinary Bladder Cancer ◽  
Structure And Function ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
And Function ◽  
Structural Significance

Abstract Single Nucleotide Polymorphisms (SNPs) help to understand the phenotypic variations in humans. Numerous studies have examined the association of SNPs with various complex diseases. Researchers have identified the association of SNPs of genes through Genome-wide association study (GWAS). A number of GWAS have identified a loci located in the TP63 gene to be significantly associated with the risk of urinary bladder cancer. However, there is not any study characterizing the SNPs located at the TP63 gene for their functional and structural significance. Hence, the study aimed to comprehensively characterize SNPs in the human TP63 gene for their functional and structural significance. We investigated and evaluated the genomic variations affecting the expression, structure, and function of the TP63 protein. The study systematically retrieved nsSNPs information for the TP63 gene from the dbSNP database. We screened and analyzed both nsSNPs and non-coding SNPs in TP63 protein using a wide variety of computational tools to find the risk of pathogenicity. A total of 17 nsSNPs were identified using the 13 bioinformatics tools (i.e., SIFT, CADD, PROVEAN, PolyPhen2, PANTHER, PhD-SNP, SNP&GO, I-Mutant 2.0, ClinVar, Mutpred2, ConSurf, HOPE, and Mutation 3D) along with domain analysis. These pathogenic mutations cause a decrease in protein stability according to I-Mutant2.0. HOPE predicted 17 SNPs to have significant effect on TP63 protein structure and function. 12 nsSNPs were found in highly conserved position in TP63 inferring the damaging effect on the structure and function of the protein. Swiss PDB Viewer showed loss of hydrogen bonds and increased energy due to the SNPs. Molecular docking showed the reduction of the binding affinity of proteins for DNA and loss of hydrogen bonds. Six non-coding SNPs were found in miRNA binding sites in gene showing the effect on protein regulation using PolymiRTS and five non-coding SNPs were identified in single tissue expression quantitative trait loci (eQTL) in lung tissue, heart tissue (LV), and cerebral hemisphere (Brain) according to GTEx portal. The characterization of nsSNPs and non-coding SNPs will support researchers to focus on TP63 gene loci and ascertain their association with certain diseases.

In Silico Identification of Novel Acute Myeloid Leukemia Associated Missense SNPs in Human CEBPA Gene

2020 ◽  
pp. 10-24
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Gene Interaction ◽  
Nucleotide Polymorphisms ◽  
Future Perspectives ◽  
Single Nucleotide ◽  
In Silico Identification ◽  
And Function ◽  
Acute Myeloid

Single nucleotide polymorphisms (SNPs) in CEBPA gene have been found to be associated with cancer especially Acute Myeloid Leukemia (AML). Therefore, the identification of functional and structural polymorphisms in CEBPA is important to study and discover therapeutics targets and potential malfunctioning. For this purpose, several bioinformatics tools were used for the identification of disease-associated nsSNPs, which might be vital for the structure and function of CEBPA, making them extremely important. In silico tools used in this study included SIFT, PROVEAN, PolyPhen2, SNP&GO and PhD-SNP, followed by ConSurf and I-Mutant. Protein 3D modelling was carried out using I-TASSER and MODELLER v9.22, while GeneMANIA and string were used for the prediction of gene-gene interaction in this regard. From our study, we found that the L345P, R333C, R339Q, V328G, R327W, L317Q, N292S, E284A, R156W, Y108N and F82L mutations were the most crucial SNPs. Additionally, the gene-gene interaction showed the genes having correlation with CEBPA’s co-expressions and importance in several pathways. In future, these 11 mutations should be investigated while studying diseases related to CEBPA, especially for AML. Being the first of its kind, future perspectives are proposed in this study, which will help in precision medicine. Animal models are of great significance in finding out CEBPA effects in disease.

Single nucleotide polymorphisms (SNPs) in human lactoferrin geneThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 381-384 ◽  
Author(s):  
Christina T. Teng ◽  
Wesley Gladwell
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Inflammatory Responses ◽  
Peer Review Process ◽  
Genome Project ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Environmental Health Sciences ◽  
Normal Healthy Individual ◽  
Lactoferrin Gene ◽  
And Function

The lactoferrin protein possesses antimicrobial and antiviral activities. It is also involved in the modulation of the immune response. In a normal healthy individual, lactoferrin plays a role in the front-line host defense against infection and in immune and inflammatory responses. Whether genomic variations, such as single nucleotide polymorphisms (SNPs), have an effect on the structure and function of lactoferrin protein and whether these variations contribute to the different susceptibility of individuals in response to environmental insults are interesting health-related issues. In this study, the lactoferrin gene was resequenced as part of the Environmental Genome Project of the National Institute of Environmental Health Sciences, which operates within the National Institutes of Health. Ninety-one healthy donors of different ethnicities were used to establish common SNPs in the exons of the lactoferrin gene in the general population. The data will serve as a basis from which study the association of lactoferrin polymorphism and disease.

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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