A Model for Metal Affinity Protein Precipitation

Abstract

We have modeled the kinetics of the metal affinity aggregation of proteins via a formalism that employs classical gelation theory in conjunction with ion binding equilibria. Simulations using our model indicate that the kinetics of coagulation are highly dependent on the pH of the solution, the pKaof the metal–ligand complex, and the molar ratio of metal ions to the metal binding sites on the protein surface. We have observed that very high metal ion concentrations and high metal–ligand binding constants serve to reduce the rate of aggregation. High proton concentrations also reduce the rate of aggregation by mass action competition with metal ions for proton binding sites. A novel post-gelation solution that incorporates a fragmentation term is used to account for the finite solubility at the end of the aggregation process. This fundamental model of the kinetics of metal affinity aggregation will help to relate aggregation process parameters to process performance.