Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin.
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2019-11
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Abstract
Inverted solubility-melting a crystal by cooling-is observed in a handful of proteins, such as carbomonoxy hemoglobin C and γD-crystallin. In human γD-crystallin, the phenomenon is associated with the mutation of the 23rd residue, a proline, to a threonine, serine, or valine. One proposed microscopic mechanism entails an increase in surface hydrophobicity upon mutagenesis. Recent crystal structures of a double mutant that includes the P23T mutation allow for a more careful investigation of this proposal. Here, we first measure the surface hydrophobicity of various mutant structures of γD-crystallin and discern no notable increase in hydrophobicity upon mutating the 23rd residue. We then investigate the solubility inversion regime with a schematic patchy particle model that includes one of three variants of temperature-dependent patch energies: two of the hydrophobic effect, and one of a more generic nature. We conclude that, while solubility inversion due to the hydrophobic effect may be possible, microscopic evidence to support it in γD-crystallin is weak. More generally, we find that solubility inversion requires a fine balance between patch strengths and their temperature-dependent component, which may explain why inverted solubility is not commonly observed in proteins. We also find that the temperature-dependent interaction has only a negligible impact on liquid-liquid phase boundaries of γD-crystallin, in line with previous experimental observations.
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Altan, Irem, Amir R Khan, Susan James, Michelle K Quinn, Jennifer J McManus and Patrick Charbonneau (2019). Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin. The journal of physical chemistry. B, 123(47). pp. 10061–10072. 10.1021/acs.jpcb.9b07774 Retrieved from https://hdl.handle.net/10161/24992.
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Patrick Charbonneau
Professor Charbonneau studies soft matter. His work combines theory and simulation to understand the glass problem, protein crystallization, microphase formation, and colloidal assembly in external fields.
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