Proteins in therapeutic formulations as well as in vivo encounter a range of cosolutes in solution. Though these solutes nearly always include dissolved salts, the effects of salts on protein kinetic stability is still only qualitatively understood. Though the Hofmeister series can be used to rank the relative effects of salts on the deactivation or stabilization of proteins, no quantitative relationship has been determined to allow prediction of protein kinetic stability in different salt solutions. Such a relationship could allow for design of improved bioprocess formulations and accelerated testing protocols for estimating the shelf-life of protein-based pharmaceuticals and biocatalyst lifetimes.

We find that the Jones-Dole B-viscosity coefficient, an indicator of ion hydration, can be used as a predictor of salt effects on the kinetic stability of model proteins. Based on this finding, we have developed a model for predicting protein deactivation in salt solutions as a function salt B-viscosity coefficients, salt concentration, and temperature. The model allows for observed protein deactivation to be expressed as a function of parameters indicative of cosolute-solvent, cosolute-protein, and protein-solvent interactions in solution. Implications of this model for designing protein formulations and accelerated evaluation of protein stability will also be considered.

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