A comprehensive In Silico analysis on the structural and functional impact of SNPs in the congenital heart defects associated with NKX2-5 gene - A molecular dynamic simulation approach

Firoz Abdul Samad, Bandar A. Suliman, Syed Hussain Basha, Thamilarasan Manivasagam, Musthafa Mohamed Essa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Congenital heart defects (CHD) presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs) in different genes have been associated with various types of congenital heart defects. NKX 2-5 gene is one among them, which encodes a homeobox-containing transcription factor that plays a crucial role during the initial phases of heart formation and development. Mutations in this gene could cause different types of congenital heart defects, including Atrial septal defect (ASD), Atrial ventricular block (AVB), Tetralogy of fallot and ventricular septal defect. This highlights the importance of studying the impact of different SNPs found within this gene that might cause structural and functional modification of its encoded protein. In this study, we retrieved SNPs from the database (dbSNP), followed by identification of potentially deleterious Nonsynonymous single nucleotide polymorphisms (nsSNPs) and prediction of their effect on proteins by computational screening using SIFT and Polyphen. Furthermore, we have carried out molecular dynamic simulation (MDS) in order to uncover the SNPs that would cause the most structural damage to the protein altering its biological function. The most important SNP that was found using our approach was rs137852685 R161P, which was predicted to cause the most damage to the structural features of the protein. Mapping nsSNPs in genes such as NKX 2-5 would provide valuable information about individuals carrying these polymorphisms, where such variations could be used as diagnostic markers.

Original languageEnglish
Article numbere0153999
JournalPLoS One
Volume11
Issue number5
DOIs
Publication statusPublished - May 1 2016

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Congenital Heart Defects
molecular dynamics
Molecular Dynamics Simulation
Polymorphism
Computer Simulation
Molecular dynamics
Genes
heart
genetic polymorphism
Defects
Computer simulation
genes
Single Nucleotide Polymorphism
Proteins
single nucleotide polymorphism
proteins
Tetralogy of Fallot
Atrial Heart Septal Defects
Homeobox Genes
Ventricular Heart Septal Defects

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A comprehensive In Silico analysis on the structural and functional impact of SNPs in the congenital heart defects associated with NKX2-5 gene - A molecular dynamic simulation approach. / Abdul Samad, Firoz; Suliman, Bandar A.; Basha, Syed Hussain; Manivasagam, Thamilarasan; Essa, Musthafa Mohamed.

In: PLoS One, Vol. 11, No. 5, e0153999, 01.05.2016.

Research output: Contribution to journalArticle

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