2026-09-20T03:28:14.793357600Zhttps://opus.uleth.ca/server/oai/requestoai:opus.uleth.ca:10133/37442019-03-27T20:27:37Zcom_10133_3346com_10133_1com_10133_296col_10133_3347col_10133_298
ULethbridge OPUS Repository
supervisor
Wetmore, Stacey D.
author
Kathuria, Preetleen
author
University of Lethbridge. Faculty of Arts and Science
2015-09-10T22:18:49Z
2015-09-10T22:18:49Z
2015
https://hdl.handle.net/10133/3744
Molecular modeling study is carried out on DNA damaged by aristolochic acids I and II. The carcinogenic effects of these acids have been attributed to the formation of bulky adducts within DNA (specifically with the adenine and guanine nucleobases). The analysis is initiated by considering the conformational preferences of the aristolochic acid adducts in small models (nucleobase, nucleoside and nucleotide) using quantum mechanical calculations. Subsequently, the adducts were studied using molecular dynamics simulations at the oligonucleotide level by incorporating the damaged base in an 11-mer DNA strand. The structural preferences of adenine and guanine adducts are compared, which may explain the experimentally-observed differential repair propensity. Finally, sequence-induced differences in the structural features of adducted DNA containing the ALI-adenine lesion are analyzed to explain the experimentally-reported higher mutagenicity of the lesion in a particular sequence. Results and implications from each of these studies are presented, and future research directions are proposed.
en_CA
adenine adducts
aristolochic acid purine adducts
computational models
density functional theory
guanine adducts
mutagenesis
Conformational analysis of DNA damaged by aristolochic acids to assess the toxicity and repair : a computational study
Thesis
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PREETLEEN_KATHURIA_MSC_2015.pdf
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PREETLEEN_KATHURIA_MSC_2015.pdf.txt