MOLECULAR-ORIGINS OF OSMOTIC 2ND VIRIAL-COEFFICIENTS OF PROTEINS

The thermodynamic properties of protein solutions are determined by th e molecular interactions involving both solvent and solute molecules. A quantitative understanding of the relationship would facilitate more systematic procedures for manipulating the properties in a process en vironment. In this work the molecular basis for the osmotic second vir ial coefficient, B-22, is studied; osmotic effects are critical in mem brane transport, and the value of B-22 has also been shown to correlat e with protein crystallization behavior. The calculations here account for steric, electrostatic, and short-range interactions, with the str uctural and functional anisotropy of the protein molecules explicitly accounted for. The orientational dependence of the protein interaction s is seen to have a pronounced effect on the calculations; in particul ar, the relatively few protein-protein configurations in which the app osing surfaces display geometric complementarity contribute disproport ionately strongly to B-22. The importance of electrostatic interaction s is also amplified in these high-complementarity configurations. The significance of molecular recognition in determining B-22 can explain the correlation with crystallization behavior, and it suggests that al teration of local molecular geometry can help in manipulating protein solution behavior. The results also have implications for the role of protein interactions in biological self-organization.