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

Publication ,  Journal Article
Altan, I; Khan, AR; James, S; Quinn, MK; McManus, JJ; Charbonneau, P
Published in: The journal of physical chemistry. B
November 2019

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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Published In

The journal of physical chemistry. B

DOI

EISSN

1520-5207

ISSN

1520-6106

Publication Date

November 2019

Volume

123

Issue

47

Start / End Page

10061 / 10072

Related Subject Headings

  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences
  • 09 Engineering
  • 03 Chemical Sciences
  • 02 Physical Sciences
 

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Altan, I., Khan, A. R., James, S., Quinn, M. K., McManus, J. J., & Charbonneau, P. (2019). Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin. The Journal of Physical Chemistry. B, 123(47), 10061–10072. https://doi.org/10.1021/acs.jpcb.9b07774
Altan, Irem, Amir R. Khan, Susan James, Michelle K. Quinn, Jennifer J. McManus, and Patrick Charbonneau. “Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin.The Journal of Physical Chemistry. B 123, no. 47 (November 2019): 10061–72. https://doi.org/10.1021/acs.jpcb.9b07774.
Altan I, Khan AR, James S, Quinn MK, McManus JJ, Charbonneau P. Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin. The journal of physical chemistry B. 2019 Nov;123(47):10061–72.
Altan, Irem, et al. “Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin.The Journal of Physical Chemistry. B, vol. 123, no. 47, Nov. 2019, pp. 10061–72. Epmc, doi:10.1021/acs.jpcb.9b07774.
Altan I, Khan AR, James S, Quinn MK, McManus JJ, Charbonneau P. Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin. The journal of physical chemistry B. 2019 Nov;123(47):10061–10072.
Journal cover image

Published In

The journal of physical chemistry. B

DOI

EISSN

1520-5207

ISSN

1520-6106

Publication Date

November 2019

Volume

123

Issue

47

Start / End Page

10061 / 10072

Related Subject Headings

  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences
  • 09 Engineering
  • 03 Chemical Sciences
  • 02 Physical Sciences