Hofmeister versus Neuberg: is ATP really a biological hydrotrope?

Recently, an interesting effect of ATP on proteins has been reported: ATP can hinder the thermal aggregation of proteins, and it can prevent fibrillation of intrinsically disorder proteins. Consequently, ATP was considered to act as a biological hydrotrope. In this paper, we demonstrate that the interactions leading to the two aforementioned phenomena are quite different from the traditionally referred hydrotropy. In the case of the increase of aggregation prevention, we show that the relevant effect is a specific ion effect of a strongly hydrated and highly charged anion in the Hofmeister series. In the case of fibrillation suppression, the most important mechanism is the interaction of adenosine with the delocalized pi-systems of amino acid residues in the protein. In regard to classical solubilization power of ATP for organic molecules, we find that ATP does not act as a classical hydrotrope, because it strongly decreases the solubility of hydrophobes.

Automated summary

ATP can hinder the thermal aggregation of proteins and prevent fibrillation of intrinsically disorder proteins, acting as a biological hydrotrope. The interactions of ATP leading to these phenomena are different from traditional hydrotropy, with specific ion effects and interactions with amino acid residues in proteins. Additionally, ATP does not act as a classical hydrotrope due to its strong decrease in the solubility of hydrophobes.