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  • Title: How Does a Hydrophobic Macromolecule Respond to a Mixed Osmolyte Environment?
    Author: Tah I, Mondal J.
    Journal: J Phys Chem B; 2016 Oct 27; 120(42):10969-10978. PubMed ID: 27700087.
    Abstract:
    The role of the protecting osmolyte trimethyl N-oxide (TMAO) in counteracting the denaturing effect of urea on a protein is quite well established. However, the mechanistic role of osmolytes on the hydrophobic interaction underlying protein folding is a topic of contention and is emerging as a key area of biophysical interest. Although recent experiments and computer simulations have established that an individual aqueous solution of TMAO and urea respectively stabilizes and destabilizes the collapsed conformation of a hydrophobic polymer, it remains to be explored how a mixed aqueous solution of protecting and denaturing osmolytes influences the conformations of the polymer. In order to bridge the gap, we have simulated the conformational behavior of both a model hydrophobic polymer and a synthetic polymer polystyrene in an aqueous mixture of TMAO and urea. Intriguingly, our free energy based simulations on both of the systems show that, even though a pure aqueous solution of TMAO stabilizes the collapsed or globular conformation of the hydrophobic polymer, addition of TMAO to an aqueous solution of urea further destabilizes the collapsed conformation of the hydrophobic polymer. We also observe that the extent of destabilization in a mixed osmolyte solution is relatively higher than that in pure aqueous urea solution. The reinforcement of the denaturation effect of the hydrophobic macromolecule in a mixed osmolyte solution is in stark contrast to the well-known counteracting role of TMAO in proteins under denaturing condition of urea. In both model and realistic systems, our results show that, in a mixed aqueous solution, a greater number of cosolutes preferentially bind to the extended conformation of the polymer relative to that in the collapsed conformation, thereby complying with the Tanford-Wyman preferential solvation theory disfavoring the collapsed conformation. The results are robust across a range of osmolyte concentrations and multiple cosolute force fields. Our findings unequivocally imply that the action of mixed osmolyte solution on hydrophobic polymer is significantly distinct from that of proteins.
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