Volume 13, Issue 1
Modeling the Influence of Salt on the Hydrophobic Effect and Protein Fold Stability

Mihir S. Date & Brian N. Dominy

Commun. Comput. Phys., 13 (2013), pp. 90-106.

Published online: 2013-01

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  • Abstract

Salt influences protein stability through electrostatic mechanisms as well as through nonpolar Hofmeister effects. In the present work, a continuum solvation based model is developed to explore the impact of salt on protein stability. This model relies on a traditional Poisson-Boltzmann (PB) term to describe the polar or electrostatic effects of salt, and a surface area dependent term containing a salt concentration dependent microscopic surface tension function to capture the non-polar Hofmeister effects. The model is first validated against a series of cold-shock protein variants whose salt-dependent protein fold stability profiles have been previously determined experimentally. The approach is then applied to HIV-1 protease in order to explain an experimentally observed enhancement in stability and activity at high (1M) NaCl concentration. The inclusion of the salt-dependent non-polar term brings the model into quantitative agreement with experiment, and provides the basis for further studies into the impact of ionic strength on protein structure, function, and evolution. 

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@Article{CiCP-13-90, author = {Mihir S. Date and Brian N. Dominy}, title = {Modeling the Influence of Salt on the Hydrophobic Effect and Protein Fold Stability}, journal = {Communications in Computational Physics}, year = {2013}, volume = {13}, number = {1}, pages = {90--106}, abstract = {

Salt influences protein stability through electrostatic mechanisms as well as through nonpolar Hofmeister effects. In the present work, a continuum solvation based model is developed to explore the impact of salt on protein stability. This model relies on a traditional Poisson-Boltzmann (PB) term to describe the polar or electrostatic effects of salt, and a surface area dependent term containing a salt concentration dependent microscopic surface tension function to capture the non-polar Hofmeister effects. The model is first validated against a series of cold-shock protein variants whose salt-dependent protein fold stability profiles have been previously determined experimentally. The approach is then applied to HIV-1 protease in order to explain an experimentally observed enhancement in stability and activity at high (1M) NaCl concentration. The inclusion of the salt-dependent non-polar term brings the model into quantitative agreement with experiment, and provides the basis for further studies into the impact of ionic strength on protein structure, function, and evolution. 

}, issn = {1991-7120}, doi = {https://doi.org/10.4208/cicp.290711.121011s}, url = {http://global-sci.org/intro/article_detail/cicp/7213.html} }
TY - JOUR T1 - Modeling the Influence of Salt on the Hydrophobic Effect and Protein Fold Stability AU - Mihir S. Date & Brian N. Dominy JO - Communications in Computational Physics VL - 1 SP - 90 EP - 106 PY - 2013 DA - 2013/01 SN - 13 DO - http://dor.org/10.4208/cicp.290711.121011s UR - https://global-sci.org/intro/cicp/7213.html KW - AB -

Salt influences protein stability through electrostatic mechanisms as well as through nonpolar Hofmeister effects. In the present work, a continuum solvation based model is developed to explore the impact of salt on protein stability. This model relies on a traditional Poisson-Boltzmann (PB) term to describe the polar or electrostatic effects of salt, and a surface area dependent term containing a salt concentration dependent microscopic surface tension function to capture the non-polar Hofmeister effects. The model is first validated against a series of cold-shock protein variants whose salt-dependent protein fold stability profiles have been previously determined experimentally. The approach is then applied to HIV-1 protease in order to explain an experimentally observed enhancement in stability and activity at high (1M) NaCl concentration. The inclusion of the salt-dependent non-polar term brings the model into quantitative agreement with experiment, and provides the basis for further studies into the impact of ionic strength on protein structure, function, and evolution. 

Mihir S. Date & Brian N. Dominy. (1970). Modeling the Influence of Salt on the Hydrophobic Effect and Protein Fold Stability. Communications in Computational Physics. 13 (1). 90-106. doi:10.4208/cicp.290711.121011s
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