Electrostatic interactions in concentrated protein solutions

TL;DR

This paper introduces an approximate model for calculating electrostatic free energy in concentrated protein solutions, combining cell models, Poisson-Boltzmann linearization, and salt partitioning to match experimental osmotic pressures and predict phase behavior.

Contribution

The paper presents a novel combined approach using a cell model and empirical modifications to accurately estimate electrostatic free energy in concentrated protein solutions.

Findings

Reproduces osmotic pressure measurements of bovine serum albumin solutions.

Predicts salt-dependent shifts in the critical temperature of lysozyme solutions.

Explains the difficulty in experimentally observing salt partitioning between phases.

Abstract

We present an approximate method for calculating the electrostatic free energy of concentrated protein solutions. Our method uses a cell model and accounts for both the coulomb energy and the entropic cost of Donnan salt partitioning. The former term is calculated by linearizing the Poisson-Boltzmann equation around a nonzero average potential, while the second term is calculated using a jellium approximation that is empirically modified to reproduce the dilute solution limit. When combined with a short-ranged binding interaction, calculated using the mean spherical approximation, our model reproduces osmotic pressure measurements of bovine serum albumin solutions. We also use our free energy to calculate the salt-dependent shift in the critical temperature of lysozyme solutions and show why the predicted salt partitioning between the dilute and dense phases has proven experimentally elusive.