Protein Solubility Calculator

The isoelectric point is the pH at which a protein has zero net charge. Near the pI, proteins often aggregate and have poor solubility because they lack electrostatic repulsion. Moving the pH away from the pI improves solubility.

Salt concentration has complex effects on protein solubility. Low salt can destabilize proteins through charge-charge interactions, while moderate salt (50-200 mM) often stabilizes proteins. Very high salt concentrations can cause precipitation through salting-out effects.

Lower temperatures generally improve protein stability and solubility by reducing thermal motion and aggregation. Most proteins are stable at 4°C for storage, while room temperature (20-25°C) is common for formulation studies.

This calculator provides a relative solubility score based on key physicochemical factors. It's useful for comparing conditions and identifying potential problems, but experimental validation is always recommended for critical applications.

Common additives include detergents (prevent aggregation), reducing agents like DTT (prevent disulfide crosslinking), and glycerol (stabilizes protein structure). The calculator accounts for these common additives in its scoring.

Yes, this calculator works for recombinant proteins. However, be aware that E. coli expression may result in inclusion bodies or misfolding, which affects solubility beyond what this calculator predicts based on sequence alone.

Try adjusting the pH further from the pI, lowering the temperature, optimizing salt concentration, or adding stabilizing additives. Consider buffer optimization, protein engineering, or co-expression with chaperones for difficult proteins.

ΔpH = pH - pI shows how far your solution pH is from the protein's isoelectric point. Values near zero indicate higher aggregation risk. Generally, |ΔpH| > 1.0 provides better solubility due to increased net charge.