Studying the effects of DNA methylation on adduct formation using molecular modeling

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nathanael K. Proctor (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Phillip Bowen

Abstract: The goal of this study was to use molecular modeling to compare and analyze the molecular structure of a double-stranded DNA fragment, and the effects of DNA methylation to adduct formation, which may eventually lead to disease-related genetic mutations. Specifically, the research work in this thesis focuses on using molecular modeling to simulate the experimental results in a recent report in which DNA adduction occurs with BPDE (benzo[a]pyrene diol epoxide) within a specific double-stranded DNA fragment that contained various methylation patterns and was quantitatively measured. The ability to use molecular modeling to correlate the pattern of DNA methylation and the locations of the most frequent adduction sites with genotoxic compounds can be very useful to further advance the study of genetic mutation, prevention of diseases, and so on. In this study the MMFF94s force field was used to run molecular dynamics simulations on dsDNA, and the results were analyzed to determine changes in the rotation of specific base pairs and the distances between the base pairs as a result of DNA methylation. The results show that there is a significant change in those two characteristics between non-methylated DNA and methylated DNA which might lead to adduct formation with BPDE.

Additional Information

Publication
Thesis
Language: English
Date: 2011
Keywords
DNA,
Subjects
Adducts, DNA
DNA $x Structure
DNA $x Methylation

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