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.