Dynamics and energetics of DNA structures and interactions studied by nuclear magnetic resonance spectroscopy

This thesis is on the study of the structure and dynamics of nucleic acids using nuclear magnetic resonance (NMR) spectroscopy.;The first section of the thesis is on investigating the strength of the hydrogen bonds in DNA. Our results show that the strength of the hydrogen bonds in the DNA molecules is equal to or greater than the strength of the hydrogen bonds in water. The nature of the base pair and the location of the base pair within the DNA sequence does not have an effect on the strength of the hydrogen bonds in B-form DNA.;The second section is on the stability of base pairs in DNA and a comparison of the stability of the base pairs to the strength of their hydrogen bonds. The base pairs in the CG 10-mer DNA were found to be slightly less stable than in the CAGA 12-mer. In addition, we did not find a correlation between the strength of the hydrogen bonds and the stability of the base pairs in the B-form DNA molecules.;In the third section, the effect of magnesium ions on the structure and dynamics of the CAGA 12-mer was investigated. The overall structure was not affected by the presence of magnesium ions, however, we did observed local dynamic changes in stability as evidenced from the imino proton exchange data of the GC base pairs. In addition, we observed site-specific binding to a GC base pair.;The final section of the thesis is on the study of the dynamics of an oxidatively damaged 8-oxoguanine (G*) lesion site in DNA, and how our results might prove or disprove the proposed models for the recognition of 8-oxoguanine. Our results on the G*C and GC dodecamers do not support either of the two proposed modes of recognition of 8-oxoguanine, namely, a Spontaneous Extrahelical Capture mechanism or an Intrahelical Energetic mechanism. The second part of this section is a comparison of the G*A and GC dodecamer base-pair opening dynamics. We propose that a repair protein would recognize a G*A base pair using either Intrahelical Energetic Recognition or an Extrahelical Capture Recognition mechanism.