Introductory Lecture: Interpreting and predicting Hofmeister salt ion and solute effects on biopolymer and model processes using the solute partitioning model

Abstract

Understanding how Hofmeister salt ions and other solutes interact with proteins, nucleic acids, other biopolymers and water and thereby affect protein and nucleic acid processes as well as model processes (e.g solubility of model compounds) in aqueous solution is a longstanding goal of biophysical research. Empirical Hofmeister salt and solute “m-values” (derivatives of the observed standard free energy change for a model or biopolymer process with respect to solute or salt concentration m3) are equal to differences in chemical potential derivatives: m-value = Δ(dμ2/dm3) = Δμ23 which quantify the preferential interactions of the solute or salt with the surface of the biopolymer or model system (component 2) exposed or buried in the process. Using the SPM, we dissect μ23 values for interactions of a solute or Hofmeister salt with a set of model compounds displaying the key functional groups of biopolymers to obtain interaction potentials (called α-values) that quantify the interaction of the solute or salt per unit area of each functional group or type of surface. Interpreted using the SPM, these α-values provide quantitative information about both the hydration of functional groups and the competitive interaction of water and the solute or salt with functional groups. The analysis corroborates and quantifies previous proposals that the Hofmeister anion and cation series for biopolymer processes are determined by ion-specific, mostly unfavorable interactions with hydrocarbon surfaces; the balance between these unfavorable nonpolar interactions and often-favorable interactions of ions with polar functional groups determine the series null points. The placement of urea and glycine betaine (GB) at opposite ends of the corresponding series of nonelectrolytes results from the favorable interactions of urea, and unfavorable interactions of GB, with many (but not all) biopolymer functional groups. Interaction potentials and local-bulk partition coefficients quantifying the distribution of solutes (e.g. urea, glycine betaine) and Hofmeister salt ions in the vicinity of each functional group make good chemical sense when interpreted in terms of competitive noncovalent interactions. These interaction potentials allow solute and Hofmeister (noncoulombic) salt effects on protein and nucleic acid processes to be interpreted or predicted, and allow the use of solutes and salts as probes of interface formation and large-scale conformational changes in the steps of a biopolymer mechanism.

Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements

“…Accordingly, the estimates of R G and R E lead to mutually consistent inferences regarding conformational preferences and the physics of coil-to-globule transitions for long homopolymers (26). A similar robustness prevails for proteins in highly denaturing environments where preferential interactions between denaturants and chain units appear to have a homogenizing effect on the pattern of intrachain interactions (3,23,(27)(28)(29), in line with the observations we report from the different methods.…”

Analysis of Strains Lacking Known Osmolyte Accumulation Mechanisms Reveals Contributions of Osmolytes and Transporters to Protection against Abiotic Stress

“…Thus, similar rankings are observed for osmoprotection and exclusion of solutes from the surface of a folded, globular protein, whereas different rankings are observed for osmoprotection and protein stabilization. This difference may reflect the different compositions of the molecular surfaces interacting with the solvent (51). Data suggest that exclusion from the outside surfaces of folded proteins, as would occur in the cytoplasm of a living cell, increases the effectiveness with which solutes rehydrate the cytoplasm (60,68).…”

“…5; the results show maximal stimulation with 100 mM TMAO, whereas other osmolytes were effective at 1 mM), and it did not stimulate growth as strongly as some other osmoprotectants that are less powerful protein stabilizers (e.g., glycine betaine) (50,51). The stimulatory effects of TMAO could have been limited by its contribution to the osmolality of the medium.…”

“…Trehalose and K ϩ glutamate (which accumulate in bacteria not offered an exogenous solute) are less strongly excluded than TMAO (69,70). The impacts of GB, proline, and TMAO on protein stability (the transition between folded and denatured states) have also been extensively documented (50,51), usually by measuring each solute's ability to protect proteins from urea-induced or thermal denaturation. TMAO is generally a more effective protein stabilizer than GB, and proline has little effect.…”

Probing the protein-folding mechanism using denaturant and temperature effects on rate constants

“…Recently, the interactions of key denaturants, osmolytes, and Hofmeister salts with the functional groups of proteins and nucleic acid have been determined, allowing these solutes to be used as thermodynamic and kinetic-mechanistic probes of the amount and the composition of the surface buried or exposed in the steps of a noncovalent protein or nucleic acid process like helix formation, folding, or binding (6)(7)(8)(9)(10)(11)(12)(13)(14). For protein folding, urea and guanidinium chloride (GuHCl) thermodynamic m-values (derivatives of the standard free energy of folding with respect to denaturant concentration) are determined almost entirely by the preferential interactions of these denaturants with the hydrocarbon and amide surface buried in folding (6):…”