Molecular thermodynamic properties of aqueous protein solutions

The intermolecular interactions of proteins in aqueous electrolyte solutions are critical to life processes and affect the design of separation procedures utilized in the biochemical and pharmaceutical industries. However, as a result of the complexity of protein molecules and the variety of intermolecular forces they exhibit, systematic design procedures for processes to separate these bio-products have been slow to develop. Previous work has employed idealized approaches that consider a number of contributions to the thermodynamic solution behavior, but that resort to parameter fitting to produce agreement with experimental data. Regardless of their limited success, these approaches should be re-examined to avoid incorrect interpretation of experimental data resulting from a flawed or incomplete model. This thesis delves into the intermolecular forces considered previously in greater detail to reveal those models' shortcomings and to take the first step toward a more realistic physical model of the protein thermodynamic solution behavior.; The protein-protein intermolecular forces considered here are the dispersion, or van der Waals, and electrostatic contributions, along with the solute excluded volume. The solute excluded volume was modeled by considering the size and positions of the atomic groups that comprise the protein, as determined by x-ray crystallography. These atomic groups were also utilized in the van der Waals formulation, in the context of colloid science and in a molecular mechanics framework. The electrostatic interactions were modeled by a colloidal approach that considers the anisotropic shape and charge distribution of the protein based on the crystallographic information.; The second virial coefficient, the first-order correction to ideal solution behavior resulting from two-body interactions, was chosen as the most appropriate measure of solution thermodynamic behavior. In accordance with the experimental conditions typically employed to measure the second virial coefficient, the McMillan-Mayer solution theory was chosen as the molecular thermodynamic framework. The steric and energetic contributions were integrated into the McMillan-Mayer solution theory to calculate the second virial coefficient. The results reveal that the long-range energetic considerations of a colloidal approach are secondary in comparison with the short-range interactions. Although the forces considered can produce a certain qualitative agreement with experimental results, there remains a need for accurate models of the short-range contributions, including ones not considered here.