Salt-containing aqueous two-phase system shows predictable partition of proteins with surface amino acids residues.

Aqueous two-phase system (ATPS) containing salts has been used for protein purification and enrichment. However, it is unclear how proteins are partitioned in the top or bottom phases of the system. In this study, we demonstrate that the partition of proteins in salt-containing ATPS (SATPS) depends only on the relation between the protein-surface amino acids and the type of salt using SATPS. The partition coefficients of four proteins changed depending on the kind of salt, according to the Hofmeister series. Interestingly, the partition coefficients of the proteins correlated to those of the combination of the amino acids in the surface of the protein with the correlation coefficients of >0.9. The results suggest that the interaction between the protein surface and aqueous ions plays an indispensable role for the partition of proteins in SATPS that can help in the design of protein partition in ATPS for purification and enrichment.