Investigation of non-covalent interactions in peptides using ion mobility mass spectrometry: Hydration, aggregation and metal ion binding of peptides

Non-covalent interactions play a critical role in protein structure and function. It is commonly accepted that biology is dominated by the chemistry of the non-covalent bonds. This dissertation is a report of efforts to understand non-covalent interactions present in peptides using ESI mass spectrometry, ion mobility spectrometry and theoretical simulation methods.; Several types of non-covalent interactions are covered in this dissertation. The first type that will be discussed is non-covalent interaction between water and peptides, i.e. peptide hydration. It is found that ionic groups offer particularly good hydration sites and that hydration properties are different for different ionic groups typically present in peptides. The fully exposed ammonium group offers the most favorable hydration site. However, in most cases the ammonium groups are partially or fully buried in the interior of peptides, which blocks their interactions with water. Another two ionic groups, the guanidinium and carboxylate groups are also good hydration sites, and they are less likely to be fully buried.{09}The presence of multiple charged sites increases the number of hydration sites, but does not enhance the hydration energy for a peptide.; Another type of non-covalent interaction that will be addressed is peptide-peptide interaction, which results in aggregation of peptides. Just as for peptide hydration, the driving force of aggregation is to stabilize the charged group in peptides. The competition between peptide aggregation and hydration is discussed.{09}The extent of aggregation or hydration depends on the relative ability of the peptide and water to stabilize the charge groups.; Finally, non-covalent interactions between metal ions and some natural hormone peptides will be discussed. In some cases, the presence of metal ions is essential for the binding of these hormone peptides to their cellular receptor. The non-covalent interaction between hormone peptides and divalent metal ions is very sensitive to the nature of the metal ions. Even though all divalent metal ions cause a dramatic conformational change in the peptides investigated, the induced structures are different for different metal ions. Thus, different metals have different biological activities.