Aggregation of biological building blocks: a theoretical and spectroscopic study

Abstract

DNA and proteins are involved in biological processes which make possible life. On the one hand, the four DNA bases constitute the alphabet of life. Their normal appearance includes stacked Watson-Crick pairs in order to form DNA strands, reinforced by the existence of the sugar backbone. However, the appearance of unusual structures, such as Hoogsteen pairs, triplexes and quadruplexes, raises the question of which are the intrinsic preferences of the DNA aggregation. On the other hand, proteins are chains of amino acids, whose interactions with DNA strands are the basis of the nucleosome formation. The mechanism which guides the nucleosome formation is still bewildering. The first goal of this thesis is the characterization of the non-covalent interactions in biological species and their aggregates by a combination of DFT calculations and Non-Covalent Interaction approach. The second goal is the elaboration of a reductionist model applying theoretical calculations, based in amino acid-DNA base interactions, in order to explain the leading mechanism of the histone-DNA formation. Finally, the third goal is the study of the intrinsic preferences of the DNA base self-aggregation process, analyzing the tautomerical landscape of the DNA bases, focusing on the competition between hydrogen bond and dispersive contributions. A combination of theoretical calculations and spectroscopic techniques has been used to understand the self-aggregation of purines (guanine) and pyrimidines (cytosine) in gas phase.