Comparison of protein structure in the crystal and in solution

Measuring and Increasing Protein Solubility

“…Green11 was also among the first to investigate protein solubility as a function of pH. Green and coworkers since have observed that solubility is minimal near the isoelectric point (p I ) of a protein, but increases as net charge increases at pH values acidic or alkaline relative to the p I 11–16. The p I is the pH value where a protein's positive and negative charges balance each other, and the protein bears a net charge of zero.…”

“…The solubility of proteins is determined by various interactions including protein–protein, protein–water, protein–ion, and ion–water interactions, and protein solubility can vary from almost complete insolubility to several hundreds of milligrams per milliliter. Extrinsic factors that determine protein solubility include ionic strength,1–4 solution composition,5–10 pH,11–16 and temperature 17–19. These extrinsic factors have been thoroughly studied and there are several excellent reviews on their effects 20–23…”

Solubility of recombinant human tissue factor pathway inhibitor

“…20,21 The net zero charge on the protein surface at its pI decreases the repulsive forces between protein molecules and makes the protein prone to precipitation. Solubility rises as net charge increases at lower pH due to the protonation of negatively charged residues, and at higher pH, because of deprotonation of positively charged residues.…”

Aqueous Solubilizing Systems for Parenteral Formulation Development—Proteins

“…pH is a key parameter that influences protein solubility (Rupley, 1968). Increasing ionization of the charged amino acids in a protein theoretically yields a more soluble protein due to increased intermolecular repulsion and increased solvation by water.…”