Date of Award


Publication Type

Doctoral Thesis

Degree Name



Chemistry and Biochemistry


Pure sciences, Alkylated nucleobases, Amide bonds, Histidyl-tRNA synthetase, Nucleic acids, Ribose


Gauld, James




Nucleic acids are biopolymers of nucleotides, which are composed of a phosphate, nucleobase and ribose sugar. In addition to acting as the genetic carrier, nucleic acids play a variety of other important roles in biological systems. In this thesis, nucleic acid-related chemistry is investigated using computational methods.

Chapter 1 presents an overview of the problems addressed in this thesis, whereas Chapter 2 discusses various theoretical methods. Then, Chapter 3 investigates the feasibility of using the phosphate oxygens as the general base to catalyze the aminoacyl transfer reaction in histidyl-tRNA synthetase. Three possible mechanisms with different phosphate oxygens acting as the base to abstract the 3'-OH group of A76 were examined and compared. Chapter 4 elucidates the catalytic mechanism of the repair of an alkylated nucleobase by the enzyme AlkB. It was found that this mechanism consists of four stages and that our calculated barrier for the rate-controlling step is in good agreement with experimental studies. Chapter 5 addresses the catalytic mechanism of the HDV ribozyme. Both cytosine and hydrated Mg2+ ion were found to be involved in the reaction with the former acting as the acid and the latter as the base. Chapter 6 studies the protonation of guanine quartets and quartet stacks. Each quartet plane was found to be able to accept maximally two protons. Chapter 7 deals with the interactions of metal ions with ribose and locked ribose. Four metal ions, Na+, K+, Mg2+ and Cd2+ were chosen and their properties upon interacting with ribose and locked ribose were compared. Chapter 8 presents the influences of the selection of computational methods and chemical models on the amide bond formation as catalyzed by the ribosome. Two proton transfer processes involving four- and six-membered transition structures were systematically examined using a variety of methods. Finally, Chapter 9 summarizes the main conclusions and possible extensions of the current work.