Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin.

Area of Science:

• Protein biophysics
• Thermodynamics of protein solutions

Background:

• Inverted solubility, where proteins crystallize upon cooling, is uncommon.
• This phenomenon is observed in certain proteins, including gammaD-crystallin.
• Mutations in human gammaD-crystallin, specifically at residue 23, are linked to inverted solubility.

Purpose of the Study:

• To investigate the proposed mechanism of increased surface hydrophobicity in gammaD-crystallin mutants exhibiting inverted solubility.
• To explore the conditions necessary for solubility inversion using a theoretical model.

Main Methods:

• Measurement of surface hydrophobicity for various gammaD-crystallin mutant structures.
• Utilizing a schematic patchy particle model with temperature-dependent patch energies to simulate solubility inversion.

Main Results:

• No significant increase in surface hydrophobicity was observed upon mutating the 23rd residue of gammaD-crystallin.
• The study found weak microscopic evidence supporting hydrophobicity as the driver for solubility inversion in gammaD-crystallin.
• The model indicated that solubility inversion requires a precise balance of interaction strengths and their temperature dependence.

Conclusions:

• The hydrophobic effect alone is unlikely to be the primary cause of solubility inversion in gammaD-crystallin.
• The rarity of inverted solubility in proteins may stem from the need for a delicate balance in interaction parameters.
• Temperature-dependent interactions have a minimal effect on liquid-liquid phase boundaries in gammaD-crystallin.