Protein precipitation by polyethylene glycol: A generalized model based on hydrodynamic radius

► Model based on PEG hydrodynamic radius corrects the errors of previous models which express PEG molecular weight explicitly. ► Predicts the effects of PEG shape, PEG size, protein size, environmental condition. ► Predictions agree reasonably well with independent solubility data. ► Selection of PEG precipitants should be based on its hydrodynamic radius, not molecular weight. PEGs for protein precipitation are usually classified by molecular weight. The higher molecular weight precipitants are more efficient but result in higher viscosity. Following empirical evidence that the precipitation efficiency is more comprehensively characterized by PEG hydrodynamic radius (rh,PEG) than molecular weight, this paper proposes a model to explicate the significance of rh,PEG. A general expression was formulated to characterize the PEG effect exclusively by rh,PEG. The coefficients of a linearized form were then fitted using empirical solubility data. The result is a simple numerical relation that models the efficiency of general-shaped PEG precipitants as a function of rh,PEG and protein hydrodynamic radius (rh,prot). This equation also explains the effects of environmental conditions and PEG branching. While predictions by the proposed correlation agree reasonably well with independent solubility data, its simplicity gives rise to potential quantitative deviations when involving small proteins, large proteins and protein mixtures. Nonetheless, the model offers a new insight into the precipitation mechanism by clarifying the significance of rh,PEG. This in turn helps to refine the selection criterion for PEG precipitants.