The Effect of pH on Protein Solubility

The effect of pH on protein solubility is significant and is one of the common variables in early screening trials. Generally, the solubility will change dramatically as pH is altered by roughly 

5 pH units however, some systems are sensitive to pH changes as small as 0. 1 pH units (Zeppenzauer 1971). The protein of interest will often dictate acceptable pH ranges for crystallization. Only pH values, which maintain the folded structure of the protein, are acceptable conditions for protein crystal growth. Unfolded structures will not crystallize and will tend to form an amorphous precipitate. 

Usually the protein solubility is minimal at the protein s isoelectric point (Ries-Kautt and Ducruix 1992), where its net charge is zero. Such behavior is predicted by a naive application of the Debye-Huckel theory for ionic solutions (Edsall 1952)  

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