Reentrant condensation of proteins in solution induced by multivalent counterions

Negatively charged globular proteins in solution undergo a condensation upon adding trivalent counterions between two critical concentrations C* and C**, C*<C**. This reentrant condensation behavior above C** is caused by short-ranged electrostatic interactions between multivalent cations and acidic residues, mechanistically different from the case of DNA. Small-angle x-ray scattering indicates a short-ranged attraction between counterion-bound proteins near C* and C**. Monte Carlo simulations (under these strong electrostatic coupling conditions) support an effective inversion of charge on surface side chains through binding of the multivalent counterions.