Modeling the Influence of Salt on the Hydrophobic Effect and Protein Fold Stability
Mihir S. Date 1, Brian N. Dominy 1*1 Department of Chemistry, Clemson University, Clemson SC 29631, USA.
Received 29 July 2011; Accepted (in revised version) 12 October 2011
Available online 12 June 2012
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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PACS: 87.15.K-, 87.15.-v
Key words: Electrostatic stability, hydrophobic effect, halophile, cold shock protein, HIV-1 protease.
Email: email@example.com (M. S. Date), firstname.lastname@example.org (B. N. Dominy)