A blast from the crystallization past, still useful today and tomorrow.

A simple method for improving protein solubility and long-term stability. Alexander P. Golovanov, Guillaume M. Hautbergue, Stuart A. Wilson, and Lu-Yun Lian. Journal of the American Chemical Society 2004 126 (29), 8933-8939. https://pubs.acs.org/doi/10.1021/ja049297h

The simultaneous addition of charged amino acids l-Arg and l-Glu at 50 mM to the buffer can dramatically increase the maximum achievable concentration of soluble protein. The Solubility & Stability Screen uses this and 95 additional unique formulations for sample buffer optimization for crystallization, cryo-electron microscopy, and NMR.

Effect of polyethylene glycol-400 at low concentrations on long term growth of muscle phosphoglucomutase crystals from concentration salt solutions. William J. Ray. Proteins: Structure, Function, and Bioinformatics 14, no. 2 (1992): 300-308. https://onlinelibrary.wiley.com/doi/abs/10.1002/prot.340140215

Low concentrations of polyethylene glycol at high salt concentrations may disrupt disordered protein aggregates and have a positive effect on nucleation efficiency and crystal growth rate. GRAS Screen 3 and GRAS Screen 4 formulations explore a library of os salts at high concentration in the presence of various polyethylene glycols at low concentration as a crystallization screen for proteins, including monoclonal antibodies and biological therapeutics.

Thermofluor-based high-throughput stability optimization of proteins for structural studies. Ericsson, Ulrika B., B. Martin Hallberg, George T. DeTitta, Niek Dekker, and Pär Nordlund. Analytical Biochemistry 357, no. 2 (2006): 289-298. https://www.sciencedirect.com/science/article/abs/pii/S0003269706005355?via%3Dihub

Using Thermofluor (Differential Scanning Fluorimetry – DSF, or Protein Thermal Shift) assays to screen and identify optimal stabilizing buffer formulation can result in a twofold increase in the number of crystallization leads. The Solubility & Stability Screen, Solubility & Stability Screen 2, and Slice pH screen protein specific reagents for optimization of sample solubility and stability.

Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Masoud Vedadi, Frank H. Niesen , Abdellah Allali-Hassani , Oleg Y. Fedorov, Patrick J. Finerty, Jr., Gregory A. Wasney, Ron Yeung, Cheryl Arrowsmith, Linda J. Ball, Helena Berglund, Raymond Hui, Brian D. Marsden , Pär Nordlund, Michael Sundstrom , Johan Weigelt, and Aled M. Edwards. PNAS vol. 103 no. 43 15835–15840. https://www.pnas.org/content/103/43/15835

Using Thermofluor (Differential Scanning Fluorimetry – DSF, or Protein Thermal Shift) and Light Scattering assays to screen and identify optimal buffer formulation to promote protein purification and/or crystallization. Silver Bullets and GRAS Additive screens are routinely used with Thermofluor and Light Scattering assays towards identifying small molecules that promote protein purification and/or crystallization.