A COMPUTATIONAL STUDY ON BIOCHEMICAL REACTIONS OF SULFUR-CONTAINING COMPOUNDS

Abstract

This thesis reports on the computational studies of biochemical reactions in two sulfur-containing systems: (1) DNA methylation by the DNA methyltransferase via nucleophilic addition of a Cysteine thiol and methyl transfer from SAM to cytosine; (2) H2S release from the reaction of a free thiol and garlic-derived organosulfur compounds. The thesis has 7 main chapters. Chapter 1 introduces the two sulfur-containing systems and the objectives of the studies. Chapter 2 describes the theoretical methods and models. Chapter 3 presents a novel 3D model of the human DNMT1-DNA complex from homology modelling and MD simulations. Chapter 4 presents a mechanistic study on the first two steps of the DNA methylation using the DFT method based on small model systems. Chapter 5 and Chapter 6 present a DFT study on H2S release from organosulfur compounds and glutathione. Chapter 7 summarizes the thesis and suggests some future work.