Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

TL;DR

This study uses computer simulations to show that the second virial coefficient in protein solutions varies non-monotonically with salt concentration, influenced by surface charge patterns, challenging classical theories and impacting protein crystallization.

Contribution

It demonstrates the significant effect of discrete surface charge patterns on protein interactions and highlights the failure of classical theories at high ionic strengths.

Findings

$B_2$ exhibits non-monotonic behavior with salt concentration.

Discrete charge patterns profoundly influence protein interactions.

Classical theories like DLVO fail at high ionic strengths.

Abstract

The osmotic virial coefficient $B_2$ of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that $B_2$ first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of $B_2$ is compared to experiments. Implications for protein crystallization are discussed.