Thermal Expansivity and AV

We can reasonably assume two major contributions to the difference in specific volume between the unfolded and folded states of a protein. The first contribution is that arising from the decrease in solvent-excluded volume when the tightly, but of course not perfectly, packed protein folded structure is disrupted. Water molecules enter this volume, thereby decreasing the overall volume of the protein solvent system. The magnitude of this contribution is a specific property of the protein, both in its folded and unfolded state. The second contribution arises from the change in the volume of the water molecules that hydrate the newly exposed protein surface area, relative to their volume in the bulk. Much of our present understanding of the contribution of differential hydration volume has come from recent studies of model compounds and proteins based on PPC. This technique, developed by Brandts and coworkers [17] and recently reviewed by us [16,18], is based on the measurement of the heat released or absorbed upon small (e.g., 0.5 MPa) pressure 

Note that the black line in Fig. 9.6a corresponds to the expansivity of pure water and that it exhibits a small negative value at low temperature. This observation helps to interpret the expansivity data. A negative expansivity 

Proteins, being composed of a combination of polar and nonpolar moieties, more or less exposed to solvent depending upon their conformation, should exhibit expansivities that correspond, in part to a weighted combination of the expansivities of these moieties. In addition, we must consider for proteins the intrinsic expansivity of the protein structure itself, in addition to the hydration, which can be positive and negative. We and Brandts and coworkers [16-18] have measured the expansivity of a few model proteins, in particular Snase, under a variety of conditions. A typical protein PPC scan is shown in Fig. 9.7a. 

It can be seen in Fig. 9.8 that the transition shifts, as expected, to higher temperature as a function of increasing osmolyte concentration. The AV decreases in absolute value from —19 to —5 ml mol-1. This is in part due to the increase in the transition temperature, and because of a positive Aa (see Fig. 9.5) the volume between the unfolded and folded state decreases in absolute value. There may be a contribution of the effect of the osmolyte to the structure of the unfolded state as well. The value of a at low temperature increases with increasing osmolyte as a result of the preferential hydration effect. At high temperature, the differences in the expansivity of the bulk water 

Onuchic, Annu. Rev. Biophys. Biomol. Struct. 35, 389 (2006) 

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