Apolar surface area

One must identify and enumerate the interactions that characterize each of the states relevant to the folding/unfolding partition function. This can be accomplished from the structure, if known, utilizing accessible polar and apolar surface area calculations and specific interactions as described below. 

The strategy used in this review to dissect specific fundamental interactions is to isolate first the hydrophobic effects and subsequently other interactions. Within this context the hydrophobic effect is defined as that contribution to the overall thermodynamics of a process that is proportional to the amount of apolar surface that becomes exposed to the solvent (Hermann, 1972 Gill and Wadso, 1976 Livingstone etal, 1991). The apolar surface area exposed to solvent can be computed using various algorithms (Lee and Richards, 1971 Hermann, 1972 Shrake and Rupley, 1973 Connolly, 1983) that yield the accessible surface area (ASA) in units of square angstroms (A2). 

With the hydrophobic effect defined as the contribution to the thermodynamics that is proportional to the exposure of apolar surface area, it is then possible for a set of homologous compounds to separate the hydrophobic contribution from all other effects by plotting any thermodynamic function (for instance, AH0) versus the number of apolar hydrogens (or the apolar surface area) that become exposed to the solvent on transfer. To the extent that the other interactions make a constant contribution to the thermodynamics,... 

These model compound studies provide us with estimates of the first two fundamental parameters of ACp ap = 0.45 cal K-1 (mol A2)-1 of buried apolar surface area and ACPjpoi = — 14.3 cal K-1 moT1 of hydrogen bonds. The average polar surface area buried per hydrogen bond in globular proteins is 54 7 A2 (see below) so that ACp>poj = - 0.26 cal K-1 (mol A2)-1 of buried polar surface. 

As discussed above, the thermodynamics of the hydrophobic effect are seen to be proportional to the apolar surface area exposed to the solvent. Based on the absence of a size dependence of AS0 on transfer... 

Analysis of the dependence of the structural thermodynamics of globular proteins on apolar surface area provides an estimation of the role of various contributions to protein stability. However, as mentioned above, proteins also show convergence temperatures that can yield similar information, given certain assumptions. 

In contrast to the relatively constant number of hydrogen bonds per residue, a set of proteins must bury variable amounts of apolar surface area in order to show convergence (Murphy and Gill, 1991). At the temperature at which the apolar contribution to AH° is zero, no variation would be observed in AH° per residue and the constant polar contribution is all that should be observed. The breakdown into polar and apolar interactions can also be viewed in terms of buried surface area. Proteins bury an increasing amount of surface area per residue with increasing size, but the increase is due to increased burial of apolar surface, whereas the polar surface buried remains constant. This is illustrated in Fig. 2 for 12 globular proteins that show convergence of AH°. These proteins bury a constant 39 2 A2 of polar... 

Fig. 2. Dependence of buried area per residue on protein size. The lines are the linear least-squares fits. The total area buried per residue increases with increasing number of residues as does the apolar surface area buried per residue. In contrast, the polar area buried per residue is independent of the size of the protein. The proteins plotted are listed in Table IV.

Equations (6)—(13) allow calculation of the free energy change at any temperature using the parameters in Table II, the number of residues, Nres, and the buried polar and apolar surface areas evaluated from the crystallographic structure using standard algorithms. The equations can be applied to the entire protein, a single domain, or to interfaces between structural elements. 

Protein A res Buried apolar surface area (A2) Buried polar surface area (A2)... 

Analysis of the crystallographic structure also reveals that the two domains interact primarily through hydrophobic and hydrogen bond interactions at the interface. The number of apolar hydrogens that become exposed on the C domain on unfolding of the N domain is 49.4, and the number of apolar hydrogens exposed on the N domain on unfolding of the C domain is 44.8. These values correspond to 726 and 659 A2 of apolar surface area, respectively. In addition, nine... 

Unlike the ion-ion PMF case, substantial apolar surface area is often buried during biomolecular conformational changes and/or complex formation. Therefore, we must also consider the apolar solvation energies discussed in a previous section. For the current example, a constant apolar coefficient method would provide an additional term for the conformational change ... 

The rather strongly favorable A values for dissolution of apolar molecules in water (Table 2.4) are surprising. They probably arise from London dispersion interactions involving a number of (small) water molecules covering the total apolar surface area. Tentative suggestions have been made that these interactions might benefit from rapid proton exchange between the waters in direct contact with the apolar solute. ... 

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