A generalized free-solvent model for the osmotic pressure of multi-component solutions containing protein–protein interactions

• The free-solvent model is generalized to account for various interactions.
• Solute–solute interactions in the form of homo- and hetero-multimers are considered.
• The model can account for any number of proteins, interactions, and species.
• The effect of the various parameters on osmotic pressure are examined.
• The limitations of the generalized free-solvent model are discussed.

The free-solvent model has been shown to have excellent predictability of the osmotic pressure for single and binary non-interactive proteins in aqueous solutions. Here the free-solvent model is extended to be more generalized by including the contributions of intra- and inter-protein interactions to the osmotic pressure of a solution in the form of homo- and hetero-multimers. The solute–solvent interactions are considered to be unique for each homo- and hetero-multimer in solution. The effect of the various generalized free-solvent model parameters on the osmotic pressure are examined for a single protein solution with a homo-dimer, a binary protein solution with no protein–protein interactions, and a binary protein solution with a hetero-dimer. Finally, the limitations associated with the generalized free-solvent model are discussed.