Osmolyte Induced Protein Behavior

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The problem tested in the experiment is whether the protein-osmolyte-water solution stabilizes or destabilizes the unfolded state of protein. This problem was used to test the mechanism by which the osmolytes, the small organic compounds, interact with the protein to affect stability. The proposed hypothesis stated that the transfer free energy of protein backbone form water to a water/osmolyte solution, Δgtr, is negatively correlated with an osmolyte’s fractional polar surface area. Δgtr is the unit used to measure the degree to which an osmolyte stabilizes the protein given that if Δgtr>0 (stabilized) and Δgtr<0 (destabilized). The independent variable was the fractional polar surface area (SA) and the dependent variable was the energy change or stability (Δgtr). The model had other two adjustable parameters or independent variables: the polar and non-polar SAs and the interaction between solvent and the protein backbone. The Δgtr was calculated using all the adjustable parameters. The first experiment involved the quantitative solvation model in which the solvent interaction energy is the function of interactant polarity. The other experiment involved the number of energetically equivalent ways of realizing a given interaction is a function of interactant surface area. To perform the experiment researchers used 1 M osmolyte solution. Using x-ray structure of eight stabilizing osmolytes calculations were performed. Even though the comparisons between the osmolyte structure and the Δgtr values indicate no evident correlation, there was a clear correlation between Δgtr and fractional surface polar area (R= 0.88). The second experiment used the quantitative model for solvent (water and osmolyte) to test the interactions with backbone polar groups. It indicated that the back-bone/osmolyte interactions became increasingly favorable as osmolyte became increasingly polar. The result stated for 1 M osmolyte concentration, the calculated and the measured Δgtr values are in good agreement. Especially as the fractional surface polar area increases, the osmolyte interaction with the protein backbone becomes increasingly favorable, that is their Δgtr values decreases. The free energy change for folding/unfolding will be linearly dependent on osmolyte concentration. The statistical mechanics model was used to calculate the average energy of the protein backbone in osmolyte solutions. Approximately 90% calculated Δgtr have the correlation exceeding 0.80. The success of the second experiment was consistent with their hypothesis.
The single amide nitrogen and two carbonyl oxygen backbone interactions were used for solvent interactions. Each of these sites had ether positive, neutral or negative charge presented by the solvent (water or osmolyte).

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