Stabilising proteins in solution using affordable and readily available small molecules

Abstract Purified proteins are sitting in a mostly aqueous environment, with normally some buffer and salt making up the conditions. This is vastly different from their natural habitat, and protein are often affected by this difference, showing signs of destabilisation or aggregation. A common method to improve the protein solubility and homogeneity is adding small molecules to the buffer conditions, as these can aid protein stability and keep the protein in solution at a concentration which is within that needed for the experiments that are to be undertaken. This review is detailing some of the small molecules that are routinely used, with a focus on them being readily available and affordable for all labs. Some of the more common small molecule additives described in this paper are (1) amino acids, like arginine or glycine, (2) sugars, like sucrose, or (3) other osmolytes, such as glycerol. The second part is covering some of the methods that can be utilised to determine whether a small molecule improves the stability of a particular protein.