The denaturing of proteins by an aqueous solution containing many types of ions is more complicated as all the ions can act, according to their Hofmeister activity, i.e., a fractional number specifying the position of the ion in the series (given previously) in terms of its relative efficiency in denaturing a reference protein.
At high salt concentrations lysozyme protein aggregation obeys the Hofmeister series originally observed by Hofmeister in the 1870s, but at low salt concentrations electrostatic interactions rather than ion dispersion forces affect protein stability resulting in the series being reversed. However, at high concentrations of salt, the solubility of the proteins drop sharply and proteins can precipitate out, referred to as "salting out".
Ion binding to carbolylic surface groups of macromolecules can either follow the Hofmeister series or the reversed Hofmeister series depending on the pH.
The concept of Hofmeister ionicity I has been invoked by Dharma-wardana et al. where it is proposed to define I  as a sum over all ionic species, of the product of the ionic concentration (mole fraction) and a fractional number specifying the "Hofmeister strength" of the ion in denaturing a given reference protein. The concept of ionicity (as a measure of the Hofmeister strength) used here has to be distinguished from ionic strength as used in electrochemistry, and also from its use in the theory of solid semiconductors.
The stability of metal ion protein binding, which affects the properties of metal cofactor-containing proteins in solution, is reflected by the Irving-Williams series.