Specific ion effects on protein fragments A dielectric spectroscopy study

Due to its relevance for biotechnological and pharmaceutical applications, the way ions interact with biomolecules and their aqueous environment is one of the most fundamental questions in solvation science. Until today, the fundamentals of our understanding of such interactions originate from the seminal work of Hofmeister in the late 1800’s, who ordered ions according to their efficiency to denature or stabilize proteins.
In the present work we provide molecular-level insight into the most fundamental questions regarding ion-protein and ion-water interactions. By using a combination of Dielectric Relaxation Spectroscopy (DRS) and Terahertz Time-Domain Spectroscopy (THz-TDS), we studied and quantified the interaction of ions with protein fragments. In our experiments we showed that denaturing ions are able to directly interact with up-to-two amide moieties, the common motif of the protein backbone, with highly denaturing cations showing the highest affinity towards the amide. The interaction strength followed a direct Hofmeister effect, apart from the guanidinium (Gdm⁺) cation, which shows an intermediate interaction strength with amide groups. Further investigation of the origins of this peculiarity suggested that it partially originates from Gdm⁺’s ability to compete with the counter-anion for the same interaction sites, as well as an enhanced affinity of Gdm⁺ to charged terminal groups.
Finally, we study ion-water interactions, focusing on how ions affect the so-called “fast” water relaxation at ~300-400 GHz in the dielectric spectra. Preliminary experiments revealed and interesting scaling of the relaxation amplitude with conductivity, which still remains a topic of study.