Ion-specificity and surface water dynamics in protein solutions.

Area of Science:

• Biophysical Chemistry
• Protein Dynamics
• Nuclear Magnetic Resonance Spectroscopy

Background:

• Ion-specific interactions at protein surfaces influence protein behavior and function.
• Understanding these effects is crucial for fields ranging from drug design to protein formulation.

Purpose of the Study:

• To investigate ion-specific effects on surface water dynamics and protein aggregation.
• To elucidate the contrasting responses of lysozyme (LZM) and bovine serum albumin (BSA) to different salt anions.
• To correlate NMR relaxation data with protein-solvent proton exchange and aggregation propensity.

Main Methods:

• Proton (1H) NMR relaxation measurements (transverse relaxation rate, R2(1H)) at 20 MHz.
• Analysis of protein-solvent proton exchange.
• 1H, 35Cl, and 14N NMR relaxation studies to probe ion binding.
• Cloud point measurements for comparison.

Main Results:

• Monovalent salt anions induced opposite trends in R2(1H) for LZM (increase) and BSA (decrease).
• The magnitude of the effect correlated with ion size and polarizability.
• Protein-solvent proton exchange showed similar contrasting effects between LZM and BSA.
• A significant increase in R2(1H) was observed to correlate with protein aggregate formation.
• NMR relaxation data successfully reproduced the salt-induced aggregation order for LZM.

Conclusions:

• The density of surface charge residues and atomic-scale surface roughness dictate protein response to salt ions.
• Ion binding and its impact on water accessibility vary significantly between proteins.
• NMR relaxation is a powerful tool for studying ion-specific effects, protein aggregation, and ion-protein interactions.