The influence of salt on processes involving aqueous proteins - Hofmeister effects

Using computer simulations we investigate the effect of specific salt ions on protein association (precipitation), denaturation, and on enzymatic activity (e.g., of HIV protease and horseradish peroxidase). As an illustrative example, our coarse-grained model of lysozyme correctly predict the reversal of Hofmeister series at the isoelctric point. Namely, for low pH, iodide is more efficient than chloride for assiciating lysozymes in water, while it is the other way around at high pH.

Binding of ions to proteins, polypeptides, and amino acids

By means of molecular dynamics and ab initio calculations we are ordering biologically relevant cations and anions in terms of their affinity to the protein surface. Simple alkali cations exhibit a propensity for the carboxylate of aspartate and glutamate and for the amide oxygen of the backbone. In both cases binding is stronger for small cations (sodium) than larger ones (potassium). For anions the situation is more complex and the lessons we are learning from the halide series are as follows. Smaller halides (flouride and chloride) interact more strongly with positively charged side chains of arginine, lysine, and protonated histidine that heavier halides (bromide and iodide).

The latter, however, exhibit an affinity for the non-polar regions of protein surface, similarly as we observed at the water/air interface. The ion-specific Hofmeister effects thus seem to be due to several physical phenomena - ion-pairing, segregation at non-polar surfaces, and others. Among the others, we are investigating the effect of ion aggregation in solution which "steals" them from the surface. This is particularly pertinent to complex molecular ions and multivalent ions, a prime example being guanidinium sulfate.

Direct and indirect radiation damage to DNA in aqueous solutions

We are approaching the basic physics and chemistry of radiation-induced damage in water. The indirect effects are due to water ionization which we follow by ab initio molecular dynamics. In particular we follow the ultrafast dynamics of both the cationic hole and excess electron created in water upon photoionization. In the realm of direct radiation damage we are attempting to accurately establish vertical ionization potentials of aqueous components of DNA and proteins by means of ab initio calculations employing a non-equilibrium polarizable continuum model.