Protein-Protein Interactions -Computational and Experimental Tools 360 positive and negative charged, polar and nonpolar amino acid residues. Finally, the size of proteins in the range of 1-5 nm (estimated by the minimal radius of a sphere containing a given mass) would significantly impact the surface charge density(8). Intermolecular interactions between protein molecules can have different origins, such as electrostatic, hydrophobic, van der waals, and hydrogen bonding (9). It is difficult

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... pinpoint the exact relative contributions from each type of interaction to the (overall) protein-protein interactions. In this review, I focus on explaining the modulations of electrostatic protein-protein interactions by the simple salt ions (shown in Figure 1 ) through their specific interactions (or binding) from both cation and anion with protein surface at salt concentrations below 0.5-1 M. In addition, the complete picture of salt ion's effects on the intermolecular interactions may be better understood by considering the following biophysical properties of proteins and salt ions: (i) the net charge, surface charge density and hydrophobicity of a protein; (ii) hydration, size, polarizability and valency of salt ions. The discussion is based on the recent experimental results reported in literature and findings from Amgen using the following experimental techniques, such as protein solubility measurement, phase transition temperature of T critical (critical temperature) or T cloud (cloud temperature) for liquid-liquid phase separation and small angle X-ray scattering (SAXS) (10-13). It has been demonstrated that there is a strong correlation between protein solubility and protein-protein interactions: protein solubility decreases when the protein-protein interactions become less repulsive or more attractive (for a protein for which its solubility increases with temperature)(12, 13). Also it is generally accepted that for a protein solution with an upper consolute point, an increase in phase transition temperature, as a result of change in the solution condition, indicates that protein-protein interactions become less repulsive or more attractive. Fig. 1. Hofmeister series adapted from (14).