Computational study of the capability of the side chains of amino acids for setting up cation···π interactions relevant in protein stability and structure

Abstract

Within every living organism, proteins carry out specific essential functions, so much that without them life would be non-viable. These molecular machines are the responsible of obtaining chemical energy and also of fabricating useful compounds for the organism itself. The interaction between cations and aromatic species in the side chains of some amino acids is one of the key factors that control the stability of proteins. Different studies suggest that this type of interaction is present in a variety of systems, pointing to its relevance in many processes of chemical and biological recognition, such as nerve transmission or transport through the membrane. Even though the interaction between cations and aromatic species is strong in the gas phase, everything seems to indicate that the environment of the interacting species may affect its characteristics, either causing changes in intensity or changes in the geometrical disposition of the interacting fragments. Considering the relevance of these interactions, the main objective of this thesis is to gain a deeper comprehension of the characteristics of systems that establish interactions between aromatic and cationic species by applying computational chemistry methods. A thorough study of this kind of interactions is performed in systems of interest, trying to clarify which are their main features. Therefore, it also aims to quantify the role played by the environment on these interactions and whether it can act as a modulator of them. Since the study of cation···π interactions is a wide field for study, this thesis is focused on interactions involving aromatic and charged species that can be on the side chain of amino acids. The results indicate that a small number of water molecules has a deep impact on the structural arrangement of the cation···π contact. The first water molecule close to the cation establishes specific interactions with the aromatic units so it is more strongly bound to the cation···π complex. Also, it has been determined that complexes of cations with aromatic amino acids tend to favour parallel arrangements of the cation over the aromatic rings, as a consequence of larger contributions of dispersion and induction which are capable of overcoming the cost of folding the amino acid.