Computational studies of damaged DNA : an investigation of DNA O-linked adducts formed due to exposure to phenolic carcinogens

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Majdi Yazdi, Mohadeseh
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Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
This thesis systematically develops a computational model to identify the conformational and base-pairing preferences of PhOdG, 4-Cl-PhOdG, DCP-OdG, TCP-OdG, and PCP-OdG by gradually increasing the size of the system also structural properties of unsubstituted O-linked. All adducts at nucleoside level adopted syn conformation. Moreover, effect of protonation at N3 and N7 site on the structural properties and deglycosilation barrier of adducted guanosine was probed. It was highly desirable to include O-linked phenolic as well as C8-dG adducts into a DNA strand in order to understand the detrimental effect of them and the conformational distortion of double helix duplex the desired modified base into NarI DNA duplex through the employment of molecular dynamic simulation (MD) was assessed. The anti-conformation against cytosine is preferred with this model for all adducts and syn conformer for all unsubstituted O-linked and ortho and para Clinked structures against guanine mismatch is the lowest energy structure.
DNA , MD simulation , C-linked adducts , DFT , O-linked adducts