Predicting the Activity Coefficients of Free-Solvent for Concentrated Globular Protein Solutions Using Independently Determined Physical Parameters

Abstract

The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.

Thermodynamic considerations in renal separation processes

“…These calculations were simplified by taking activity coefficients as unity, based on a review of available data [ 18 , 24 , 37 ]. Better approximations for the activity coefficients are required to obtain results that are more accurate.…”

Interrogating the Osmotic Pressure of Self-Crowded Bovine Serum Albumin Solutions: Implications of Specific Monovalent Anion Effects Relative to the Hofmeister Series

“…[46][47][48][49][50][51] However, we have shown that, via our FSB model, the bulk property, osmotic pressure, of self-crowded proteins and crowded binary globular protein solutions can directly provide ion binding and hydration properties of proteins, specifically in the highly crowded regions where the rate of change of osmotic pressure to protein concentration is highly non-linear. [52][53][54][55][56][57][58][59][60][61][62][63] Because the FSB model focuses on protein hydration and ion-binding, it can provide a fortuitous approach in interrogating anion effects on crowded protein solutions.…”

“…Osmotic pressure does not give direct crystallization information. Nevertheless, a number of researchers have used osmotic pressure to address observed phenomena of proteins in ionic aqueous solutions via protein–protein interactions. − However, we have shown that via our FSB model, the bulk property, osmotic pressure of self-crowded proteins and crowded binary globular protein solutions can directly provide ion binding and hydration properties of proteins, specifically in the highly crowded regions where the rate of change of osmotic pressure to protein concentration is highly nonlinear. − Because the FSB model focuses on protein hydration and ion binding, it can provide a fortuitous approach in interrogating anion effects on crowded protein solutions.…”

Mathematical modeling of the batch adsorption of proteins on new restricted access media with poly(ethylene glycol) as a semi-permeable barrier using compact finite differences

“…Protein molecular diffusivity was assumed constant since the working protein conditions can still be considered as dilute such that the respective activity coefficient can be set to 1.0, making the molecular diffusivity independent of protein concentration (McBride and Rodgers, 2013).…”