Prediction of Hofmeister ion effects on biopolymer processes

At moderate to high concentrations, salt ions exert a wide range of effects on protein folding and other protein processes, from extremely destabilizing (GuH+, SCN-) to very stabilizing (SO42-). The Hofmeister series is a qualitative ranking of these effects, originally based on the effectiveness of salts as protein precipitants and subsequently observed for other processes including creating air-water surface and dissolving hydrocarbons in water. Recently surface spectroscopy, molecular dynamics simulations and molecular thermodynamic analysis of surface tension and model compound solubility data have all provided evidence that local accumulation or exclusion of individual salt ions, relative to bulk concentrations, is responsible for their Hofmeister effects. In particular, application of a novel two-domain salt ion partitioning model (SPM) to analyze effects of Hofmeister salts on the surface tension of water and on hydrocarbon and peptide solubility (Pegram & Record, J. Phys. Chem. B 112, 9428 (2008); 111, 5411 (2007)) provides a quantitative molecular thermodynamic description of the individual partitioning of salt cations and anions at uncharged interfaces, with predictive capability. This analysis shows that the Hofmeister rank order of ions arises from their interactions with nonpolar surface. Surface-bulk partition coefficients of ions obtained from hydrocarbon and amide model compound solubility data, together with a coarse-grained description of functional groups that make up molecular surfaces, allow the quantitative prediction of Hofmeister (noncoulombic) salt effects on micelle formation, protein folding, protein crystallization and DNA helix formation.This work is supported by NIH GM47022.