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Molecular thermodynamics for salt-induced protein precipitation

Journal Article · · AIChE Journal
; ; ;  [1]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Chemical Engineering

In research laboratories and in the biotechnology industry, precipitation is commonly used to separate and isolate proteins from solutions. A molecular-thermodynamic model is developed for salt-induced protein precipitation, which considers on aqueous solution of globular protein molecules as a pseudo-one-component system containing macroions that interact through Coulombic repulsion, dispersion attraction and hydrophobic interactions, and forces arising from ion-excluded volume. Forces from ion-excluded volume take into account formation of ion pairs and ionic clusters at high salt concentrations; they are calculated in the context of the Percus-Yevick integral-equation theory. Hydrophobic interactions between exposed nonpolar amino-acid residues on the surfaces of the protein molecules are modeled as short-range, attractive interactions between ``spherical caps`` on the surfaces of the protein polyions. An equation of state is derived using perturbation theory. From this equation of state the authors calculate liquid-liquid equilibria: equilibrium between an aqueous phase dilute in protein and another aqueous phase rich in protein, which represents ``precipitated`` protein. In the equation of state, center-to-center, spherically symmetric macroion-macroion interactions are described by the random-phase approximation, while the orientation-dependent short-range hydrophobic interaction is incorporated through the perturbation theory of associating fluids. The results suggest that either ion-excluded-volume or hydrophobic-bonding effects can precipitate proteins in aqueous solutions with high salt concentrations.

OSTI ID:
116290
Journal Information:
AIChE Journal, Journal Name: AIChE Journal Journal Issue: 9 Vol. 41; ISSN AICEAC; ISSN 0001-1541
Country of Publication:
United States
Language:
English

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