Computational studies on DNA: insights into structure and dynamics

The best-characterized epigenetic modification is DNA methylation, which was found to shape significantly gene expression in mammalian cells, though bacteria and plants display less sequence specificity. The cytosine methylation of DNA sequence here was studied by the molecular dynamic (MD) metho...

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Autor principal: Kanna, Charan Raju
Formato: H2
Lenguaje:Inglés
Publicado: SLU/Department of Plant Biology (from 140101) 2015
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author Kanna, Charan Raju
author_browse Kanna, Charan Raju
author_facet Kanna, Charan Raju
author_sort Kanna, Charan Raju
collection Epsilon Archive for Student Projects
description The best-characterized epigenetic modification is DNA methylation, which was found to shape significantly gene expression in mammalian cells, though bacteria and plants display less sequence specificity. The cytosine methylation of DNA sequence here was studied by the molecular dynamic (MD) method. We found that the optimized structures are not significantly altered between unmethylated, methylated sequences. However, sampling of the molecule dynamical landscape via long MD simulations showed that the altered sequences could adopt different conformations (revealed in the twist and roll angles) from the unmodified DNA, which are dependent on the §sequence environment. We propose that this conformational diversity may play a role on protein recognition. The G-rich sequences are studied with MD simulations to check the propensity of the sequence to adopt to A-form or B-form of DNA. The results showed that the DNA sequence adopts most of the time in A-form and also spend sometime in between A-form and B-form. The groove widths showed the conformation in B-form. By analyzing the DNA in different contexts using computational methods we were able to test limits that force field methods offer for these systems. We propose that this conformational diversity may play a role in protein recognition. Finally, we have studied the conformational changes of DNA sequence with uracil as a base. Sometimes in the replication process uracil can be formed and the mismatch base pair in the DNA sequence is removed by the enzyme UDG (Uracil-DNA sequence). In the present work MD simulations were used to study the structure, dynamics and base pair kinetics of DNA sequence. The opening and closing kinetics of the T-A base pair were studied. A fast base pair opening was observed and also additionally base flipping was spotted. A very fast opening of the bases may be responsible for the fast closing of the bases. In order to characterize the complete study of base pair kinetics in relation to T-A versus U-A base pairs is currently under way.
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institution Swedish University of Agricultural Sciences
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publishDate 2015
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spelling RepoSLU87252016-01-18T15:07:18Z Computational studies on DNA: insights into structure and dynamics Kanna, Charan Raju epigenetic modifications DNA methylation G-rich sequence uracil molecular dynamics demethylation The best-characterized epigenetic modification is DNA methylation, which was found to shape significantly gene expression in mammalian cells, though bacteria and plants display less sequence specificity. The cytosine methylation of DNA sequence here was studied by the molecular dynamic (MD) method. We found that the optimized structures are not significantly altered between unmethylated, methylated sequences. However, sampling of the molecule dynamical landscape via long MD simulations showed that the altered sequences could adopt different conformations (revealed in the twist and roll angles) from the unmodified DNA, which are dependent on the §sequence environment. We propose that this conformational diversity may play a role on protein recognition. The G-rich sequences are studied with MD simulations to check the propensity of the sequence to adopt to A-form or B-form of DNA. The results showed that the DNA sequence adopts most of the time in A-form and also spend sometime in between A-form and B-form. The groove widths showed the conformation in B-form. By analyzing the DNA in different contexts using computational methods we were able to test limits that force field methods offer for these systems. We propose that this conformational diversity may play a role in protein recognition. Finally, we have studied the conformational changes of DNA sequence with uracil as a base. Sometimes in the replication process uracil can be formed and the mismatch base pair in the DNA sequence is removed by the enzyme UDG (Uracil-DNA sequence). In the present work MD simulations were used to study the structure, dynamics and base pair kinetics of DNA sequence. The opening and closing kinetics of the T-A base pair were studied. A fast base pair opening was observed and also additionally base flipping was spotted. A very fast opening of the bases may be responsible for the fast closing of the bases. In order to characterize the complete study of base pair kinetics in relation to T-A versus U-A base pairs is currently under way. SLU/Department of Plant Biology (from 140101) 2015 H2 eng https://stud.epsilon.slu.se/8725/
spellingShingle epigenetic modifications
DNA methylation
G-rich sequence
uracil
molecular dynamics
demethylation
Kanna, Charan Raju
Computational studies on DNA: insights into structure and dynamics
title Computational studies on DNA: insights into structure and dynamics
title_full Computational studies on DNA: insights into structure and dynamics
title_fullStr Computational studies on DNA: insights into structure and dynamics
title_full_unstemmed Computational studies on DNA: insights into structure and dynamics
title_short Computational studies on DNA: insights into structure and dynamics
title_sort computational studies on dna: insights into structure and dynamics
topic epigenetic modifications
DNA methylation
G-rich sequence
uracil
molecular dynamics
demethylation