For more than a century, urea has been widely used as an agent for protein denaturation. The mechanism of how protein unfolds is not well understood and been reviewed by researchers of physical, chemical and biological sciences. In this paper, we focus on this historical puzzle through a pure physical point of view. We have used 15 model molecules to mimic protein backbone and side chains. The solvation free energies and enthalpic/entropic decompositions of these 15 molecules were calculated in three electrolytes: aqueous urea and NaCl solutions and pure water. We have successfully reproduced the salting-out effect of NaCl and salting-in effect of urea on protein models. By carefully analysis of the thermodynamics properties of the salting process, the salting-effect is found to be enthalpy driven for both NaCl and urea. The attraction force between urea and protein models is dominated by van der Waals interaction. This observation challenges the hydrogen-bonding driven mechanism for the protein unfolding proposed previously.

Salting effects on protein components in aqueous NaCl and urea solutions: Toward urea induced protein denaturation

243rd National Meeting (2012)

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