Solubility as a function of protein structure and solvent components

This review deals with ways of stabilizing proteins against aggregation and with methods to determine, predict, and increase solubility. Solvent additives (osmolytes) that stabilize proteins are listed with a description of their effects on proteins and on the solvation properties of water. Special attention is given to areas where solubility limitations pose major problems, as in the preparation of highly concentrated solutions of recombinant proteins for structural determination with NMR and X-ray crystallography, refolding of inclusion body proteins, studies of membrane protein dynamics, and in the formulation of proteins for pharmaceutical use. Structural factors relating to solubility and possibilities for protein engineering are analyzed.