Application of protein crystallization methodologies to enhance the solubility, stability and monodispersity of proteins

Protein crystallization screens are commonly used to find specific crystallization conditions. In practice, undesirable clear drops are often ignored. We hypothesize that clear drops may be potentially useful for finding the conditions leading to proteins with high solubility and monodispersity. Based on this idea, we first tested three model proteins and confirmed that improved monodispersity could be observed in the clear drops. Next, we used this strategy to achieve the maximum solubility and monodispersity of a new protein (RNA binding motif 3, RBM3). We suggest that this strategy is useful not only for high-throughput screening of optimal solubilization conditions but also for screening of biopharmaceutical formulations.