PMID- 27152669
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20190219
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - 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.
PG  - e0153999
LID - 10.1371/journal.pone.0153999 [doi]
LID - e0153999
AB  - 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 Non-synonymous 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.
FAU - Abdul Samad, Firoz
AU  - Abdul Samad F
AD  - Center for Genetics and Inherited Diseases, Taibah University, Madinah, Kingdom 
      of Saudi Arabia.
FAU - Suliman, Bandar A
AU  - Suliman BA
AD  - Center for Genetics and Inherited Diseases, Taibah University, Madinah, Kingdom 
      of Saudi Arabia.
AD  - Molecular Biomedicine Program, Research Center, King Faisal Specialist Hospital & 
      Research Center, Riyadh, Kingdom of Saudi Arabia.
FAU - Basha, Syed Hussain
AU  - Basha SH
AD  - Innovative Informatica Technologies, HIG, HUDA, Mayuri Nagar, Miyapur, Hyderabad, 
      500 049, India.
FAU - Manivasagam, Thamilarasan
AU  - Manivasagam T
AD  - Department of Biochemistry and Biotechnology, Annamalai University, Annamalai 
      Nagar, Tamilnadu, India.
FAU - Essa, Musthafa Mohamed
AU  - Essa MM
AUID- ORCID: 0000-0001-7505-9785
AD  - Department of Food Science and Nutrition, College of Agricultural and Marine 
      Sciences, Sultan Qaboos University, Muscat, Oman.
AD  - Aging and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160506
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Homeobox Protein Nkx-2.5)
RN  - 0 (NKX2-5 protein, human)
SB  - IM
MH  - Computer Simulation
MH  - Heart Defects, Congenital/*genetics
MH  - Homeobox Protein Nkx-2.5/chemistry/*genetics
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Molecular Dynamics Simulation
MH  - Mutation
MH  - *Polymorphism, Single Nucleotide
MH  - Protein Conformation
PMC - PMC4859487
COIS- Competing Interests: Innovative Informatica Technologies does not alter the 
      adherence of PLOS ONE policies on sharing data and materials.
EDAT- 2016/05/07 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/05/06
CRDT- 2016/05/07 06:00
PHST- 2016/01/14 00:00 [received]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/05/07 06:00 [entrez]
PHST- 2016/05/07 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/05/06 00:00 [pmc-release]
AID - PONE-D-16-01571 [pii]
AID - 10.1371/journal.pone.0153999 [doi]
PST - epublish
SO  - PLoS One. 2016 May 6;11(5):e0153999. doi: 10.1371/journal.pone.0153999. 
      eCollection 2016.