title: Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility.
abstract: Protein solubility is a problem for many protein chemists, including structural biologists and developers of protein pharmaceuticals. Knowledge about how intrinsic factors influence solubility is limited due to the difficulty of obtaining quantitative solubility measurements. Solubility measurements in buffer alone are difficult to reproduce, because gels or supersaturated solutions often form, making it impossible to determine solubility values for many proteins. Protein precipitants can be used to obtain comparative solubility measurements and, in some cases, estimations of solubility in buffer alone. Protein precipitants fall into three broad classes: salts, long-chain polymers, and organic solvents. Here, we compare the use of representatives from two classes of precipitants, ammonium sulfate and polyethylene glycol 8000, by measuring the solubility of seven proteins. We find that increased negative surface charge correlates strongly with increased protein solubility and may be due to strong binding of water by the acidic amino acids. We also find that the solubility results obtained for the two different precipitants agree closely with each other, suggesting that the two precipitants probe similar properties that are relevant to solubility in buffer alone.
authors: Department of Biochemistry and Biophysics, Texas A&M Health Science Center, Texas A&M University, College Station, Texas, USA.
authors: Ryan M
authors: RM
authors: Kramer
authors: Varad R
authors: VR
authors: Shende
authors: Nicole
authors: N
authors: Motl
authors: C Nick
authors: CN
authors: Pace
authors: J Martin
authors: JM
authors: Scholtz
mesh_terms: D000645:Ammonium Sulfate / Q000737:chemistry; D000818:Animals; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties
chemical_list: D011506:Proteins; D011092:Polyethylene Glycols; D000645:Ammonium Sulfate