Computational investigation of nucleic acids.

Abstract

In this work, various computational chemistry models are applied to problems of biochemical interest, with emphasis on nucleic acids. First various density functionals and multilevel methods are benchmarked against experimental proton affinities and gas-phase basicities. Then prediction of biologically relevant values of nucleic acids, amino acids, RNA sugar, and phosphates are made. In applied work, density functional theory is employed to help elucidate topics in lesion formation in nucleic acids. In particular the role of C5 methyl cytosine substitution is investigated. <DISS_para>through the use of various analogues and explaining NMR spectra of specific adenine lesions formed by 1,2,3,4-diepoxybutane. Finally, two works related to parameterization are given. The first is CHARMM molecular mechanical force field parameter development for the reactive intermediates of native and thio-substituted ribozymes. This work provides modifications necessary to reproduce structural aspects of transition state structures during phosphate transesterification. The second is an investigation into the appropriate solvation free energy for phosphoric acid and its anions. This includes both a review of the currently used and available data as well as a benchmark of various computational solvation models.