Hofmeister Effects
Understanding the molecular mechanisms of ion specific effects on proteins in aqueous environments is important for understanding myriad biological processes including ion regulation, cell signaling, protein folding, and enzyme catalysis. These processes are greatly influenced by ion-protein interactions. As such, they require direct investigation at the molecular level. Aqueous salt solutions affect the behavior of proteins in a recurring trend known as the Hofmeister series. First discovered in 1888, the Hofmeister series ranks anions and cations in order of their ability to precipitate proteins from aqueous solutions. Na+ and Cl– typically divide the series (see Fig. 1).
In our laboratory, NMR, Raman, FT-IR and Non-linear Spectroscopy studies along with ITC, DSC, and temperature gradient microfluidic measurements were utilized to investigate the effects of ions on model biomolecules and biopolymers.
We have investigated the effect of electrolytes on the folding of proteins and colloidal structures in aqueous solution (JACS, 135, 2013, 5062-5067, pdf; JACS, 134, 2012, 10039-10046, pdf; JACS, 131, 2009, 15188-15193, pdf; JACS, 129, 2007, 12272-12279, pdf). Large, soft anions such as SCN– and I– were found to bind to the backbone of proteins while smaller, harder anions such as SO42- and Cl– were found to be excluded. Weakly hydrated cations such as Na+ and K+ are also excluded while Mg2+, Ca2+, and Li+ only weakly partition to the amide oxygen in protein backbones. The identification of these molecular level binding sites provide new insights into the mechanism of electrolyte-specific effects on protein folding, aggregation, and enzymatic catalysis.
In closely connected studies, we have explored the mechanism by which osmolytes can denature or stabilize folded proteins (JACS, 133, 2011, 18707-18712, pdf; JACS, 131, 2009, 9304-9310, pdf; JACS, 129, 2007, 15104-15105, pdf). In contrast to Hofmeister salts, osmolytes are often present in solution at much higher concentrations. There has been a long standing question as to whether the mechanism by which osmoltyes affect biomacromolecules is direct or indirect (via its influence on water structure). Again, a combination of spectroscopic and thermodynamic techniques has been employed in our laboratory to investigate this problem.