On the relationship between the solubility of proteins and the osmotic second virial coefficient

Abstract

-A relationship between the osmotic second virial coefficient of proteins in aqueous salt solutions, the solubility of proteins in these solutions and the salt concentration is presented. The model developed considers that the solid-liquid equilibrium is established with neutral protein molecules and that the relationship between the protein solubility and the salt concentration follows Cohn's equation. The validity of the model is restricted to the salting-out region of the phase diagrams, which is the situation of greater practical importance. The resulting equations were successfully applied to systems containing lysozyme and ovalbumin.

A coarse-grained xDLVO model for colloidal protein–protein interactions

“…The potential of mean force in xDLVO-CG, calculated according to eqn (11) and depicted in Fig. 4, consists of interaction potentials of different salt induced dependencies.…”

“…1 in Appendix) and implemented according to eqn (13), and by the Lennard-Jones potential (in red) from the shape-based coarse-grained model (xDLVO-CG(LJ)). The B 22 coefficients for LYZ at pH 7 and Subs at pH 5.5 using both potentials, eqn (11), are shown correspondingly on the right panel.…”

“…Here, the most relevant quantity is the second virial coefficient, known in diluted systems as B 22 , which gives information about average two-body interactions between protein molecules. B 22 is a measure of the non-specific protein binding capacity 6 and stickiness, and it has been investigated widely as a semi-quantitative approach to characterize protein solubility, [7][8][9][10][11][12] phase behavior [13][14][15][16] and crystallization. 2,7,9,[16][17][18] Positive values of the B 22 coefficient indicate the dominance of repulsion interactions between proteins and correspond to good protein solubility.…”

“…7,8,20 Since then, several empirical models were proposed aiming to correlate B 22 quantitatively with solubility and self-assembly with parameters fitted from experimental data. 11,18,21 Moreover, thermodynamic relations between the protein solubility and B 22 were developed, 7,12 where the solubility, S, is calculated from the measured B 22 using:…”

Mapping the mAb Aggregation Propensity Using Self-Interaction Chromatography as a Screening Tool

“…There has been significant research devoted to correlating B 22 with different solution properties which are indicative of the protein solution behavior, including protein solubility, crystallization, phase behavior, and formulation conditions. A number of thermodynamic-based solubility models has been presented and directly verified with experimental data, − while other papers have taken an experimentally led approach and established a correlation between B 22 and solubility. , The use of B 22 to determine the phase behavior and crystallization conditions has also been widely reported for different proteins with varying levels of success, , and similarly, it was shown to quickly screen formulation conditions . Improvements in SIC include operational speed, the application of microfluidic chips, and microcolumns with low levels of protein.…”