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

Single nucleotide polymorphisms (SNPs) help to understand the phenotypic variations in humans. Genome-wide association studies (GWAS) have identified SNPs located in the tumor protein 63 (TP63) locus to be associated with the genetic susceptibility of cancers. However, there is a lack of in-depth ch...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shamima Akter, Shafaat Hossain, Md. Ackas Ali, Md. Ismail Hosen, Hossain Uddin Shekhar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TP63 nsSNPs non-coding SNPs dbSNP MD simulations molecular docking Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/28a9703c0e554456a2840af475bf0921
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:28a9703c0e554456a2840af475bf0921
record_format	dspace
spelling	oai:doaj.org-article:28a9703c0e554456a2840af475bf09212021-11-25T16:54:38ZComprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools10.3390/biom111117332218-273Xhttps://doaj.org/article/28a9703c0e554456a2840af475bf09212021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1733https://doaj.org/toc/2218-273XSingle nucleotide polymorphisms (SNPs) help to understand the phenotypic variations in humans. Genome-wide association studies (GWAS) have identified SNPs located in the tumor protein 63 (TP63) locus to be associated with the genetic susceptibility of cancers. However, there is a lack of in-depth characterization of the structural and functional impacts of the SNPs located at the <i>TP63</i> gene. The current study was designed for the comprehensive characterization of the coding and non-coding SNPs in the human <i>TP63</i> gene for their functional and structural significance. The functional and structural effects of the SNPs were investigated using a wide variety of computational tools and approaches, including molecular dynamics (MD) simulation. The deleterious impact of eight nonsynonymous SNPs (nsSNPs) affecting protein stability, structure, and functions was measured by using 13 bioinformatics tools. These eight nsSNPs are in highly conserved positions in protein and were predicted to decrease protein stability and have a deleterious impact on the TP63 protein function. Molecular docking analysis showed five nsSNPs to reduce the binding affinity of TP63 protein to DNA with significant results for three SNPs (R319H, G349E, and C347F). Further, MD simulations revealed the possible disruption of TP63 and DNA binding, hampering the essential protein function. PolymiRTS study found five non-coding SNPs in miRNA binding sites, and the GTEx portal recognized five eQTLs SNPs in single tissue of the lung, heart (LV), and cerebral hemisphere (brain). Characterized nsSNPs and non-coding SNPs will help researchers to focus on <i>TP63</i> gene loci and ascertain their association with certain diseases.Shamima AkterShafaat HossainMd. Ackas AliMd. Ismail HosenHossain Uddin ShekharMDPI AGarticleTP63nsSNPsnon-coding SNPsdbSNPMD simulationsmolecular dockingMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1733, p 1733 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TP63 nsSNPs non-coding SNPs dbSNP MD simulations molecular docking Microbiology QR1-502
spellingShingle	TP63 nsSNPs non-coding SNPs dbSNP MD simulations molecular docking Microbiology QR1-502 Shamima Akter Shafaat Hossain Md. Ackas Ali Md. Ismail Hosen Hossain Uddin Shekhar Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
description	Single nucleotide polymorphisms (SNPs) help to understand the phenotypic variations in humans. Genome-wide association studies (GWAS) have identified SNPs located in the tumor protein 63 (TP63) locus to be associated with the genetic susceptibility of cancers. However, there is a lack of in-depth characterization of the structural and functional impacts of the SNPs located at the <i>TP63</i> gene. The current study was designed for the comprehensive characterization of the coding and non-coding SNPs in the human <i>TP63</i> gene for their functional and structural significance. The functional and structural effects of the SNPs were investigated using a wide variety of computational tools and approaches, including molecular dynamics (MD) simulation. The deleterious impact of eight nonsynonymous SNPs (nsSNPs) affecting protein stability, structure, and functions was measured by using 13 bioinformatics tools. These eight nsSNPs are in highly conserved positions in protein and were predicted to decrease protein stability and have a deleterious impact on the TP63 protein function. Molecular docking analysis showed five nsSNPs to reduce the binding affinity of TP63 protein to DNA with significant results for three SNPs (R319H, G349E, and C347F). Further, MD simulations revealed the possible disruption of TP63 and DNA binding, hampering the essential protein function. PolymiRTS study found five non-coding SNPs in miRNA binding sites, and the GTEx portal recognized five eQTLs SNPs in single tissue of the lung, heart (LV), and cerebral hemisphere (brain). Characterized nsSNPs and non-coding SNPs will help researchers to focus on <i>TP63</i> gene loci and ascertain their association with certain diseases.
format	article
author	Shamima Akter Shafaat Hossain Md. Ackas Ali Md. Ismail Hosen Hossain Uddin Shekhar
author_facet	Shamima Akter Shafaat Hossain Md. Ackas Ali Md. Ismail Hosen Hossain Uddin Shekhar
author_sort	Shamima Akter
title	Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
title_short	Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
title_full	Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
title_fullStr	Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
title_full_unstemmed	Comprehensive Characterization of the Coding and Non-Coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools
title_sort	comprehensive characterization of the coding and non-coding single nucleotide polymorphisms in the tumor protein p63 (tp63) gene using in silico tools
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/28a9703c0e554456a2840af475bf0921
work_keys_str_mv	AT shamimaakter comprehensivecharacterizationofthecodingandnoncodingsinglenucleotidepolymorphismsinthetumorproteinp63tp63geneusinginsilicotools AT shafaathossain comprehensivecharacterizationofthecodingandnoncodingsinglenucleotidepolymorphismsinthetumorproteinp63tp63geneusinginsilicotools AT mdackasali comprehensivecharacterizationofthecodingandnoncodingsinglenucleotidepolymorphismsinthetumorproteinp63tp63geneusinginsilicotools AT mdismailhosen comprehensivecharacterizationofthecodingandnoncodingsinglenucleotidepolymorphismsinthetumorproteinp63tp63geneusinginsilicotools AT hossainuddinshekhar comprehensivecharacterizationofthecodingandnoncodingsinglenucleotidepolymorphismsinthetumorproteinp63tp63geneusinginsilicotools
_version_	1718412826546012160

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

Ejemplares similares