Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.

<h4>Background</h4>Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mu...

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Autores principales: C George Priya Doss, N Nagasundaram
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:c7d0743bc3d840ad9340024731ceb2242021-11-18T07:26:43ZInvestigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.1932-620310.1371/journal.pone.0031677https://doaj.org/article/c7d0743bc3d840ad9340024731ceb2242012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22384055/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA.<h4>Principal findings</h4>In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis.<h4>Significance</h4>Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis.C George Priya DossN NagasundaramPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31677 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
C George Priya Doss
N Nagasundaram
Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
description <h4>Background</h4>Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA.<h4>Principal findings</h4>In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis.<h4>Significance</h4>Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis.
format article
author C George Priya Doss
N Nagasundaram
author_facet C George Priya Doss
N Nagasundaram
author_sort C George Priya Doss
title Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
title_short Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
title_full Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
title_fullStr Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
title_full_unstemmed Investigating the structural impacts of I64T and P311S mutations in APE1-DNA complex: a molecular dynamics approach.
title_sort investigating the structural impacts of i64t and p311s mutations in ape1-dna complex: a molecular dynamics approach.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/c7d0743bc3d840ad9340024731ceb224
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AT nnagasundaram investigatingthestructuralimpactsofi64tandp311smutationsinape1dnacomplexamoleculardynamicsapproach
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