Unfolded and folded states

Fig. 5 Schematic representation of doubly spin-labeled phenylene ethynylene oligomer in the unfolded and folded states, showing the increased proximity of the spin labels in the folded state vs the unfolded state...

We note here that while A/3, the difference in compressibility between the unfolded and folded state, necessarily plays a role at high temperature and pressure,... 

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... 

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... 

The fractions of the population in the unfolded and folded states at equilibrium for the TTM are given by eq 2, and the free energy of folding is given by eq 3 (the last term is specific to the TTM). 

Figure 12 Free energy surfaces for protein A computed with REMD simulations, (a) shows the surface as a function of RMSD and the number of native contacts below the folding transition temperature. The native state shows two basins corresponding to a hydrated nearly folded state and to the dry folded state, (b) shows the surface as a function of RMSD and the number of native contacts at the folding transition temperature. The unfolded and folded states are equally populated at this temperature. Taken with permission from Garcia and Onuchic. ...

The difference in heat capacity between the unfolded and folded states (kJ/mol K) Fractional siuface coverage (dimensionless)... 

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