Principles of Protein Structure - H. Schiltz 1982

Thermodynamics and Kinetics of Polypeptide Chain Folding
Thermodynamic Aspects
Balance of Energetic Contributions in a Globular Protein

Globular Proteins are precisely balanced systems. The estimates given above provide insight into the balance of thermodynamic contributions. However, this balance is incomplete because the ΔG_pacтв contribution is missing. For the example considered, the value of ΔG_рaств is quite small, since helix formation results in the removal of only the polar backbone from the solvent, rather than large hydrophobic side chains (Sec. 3.5).

Let us now consider an "average" globular protein consisting of 150 amino acid residues. As follows from equation (8.1), the T ∙ ΔS value in this case amounts to several hundred kilocalories per mole. To bring the peptide chain and side chains into their native conformation, this energy must be compensated by The values of ΔG_рacтв and ΔH_цепь (equation (3.2)). Judging by the number of residues removed from the solvent and the Free energy contributions of this process (Fig. 1.8), the value of ΔG_рaств is at least 100 kcal/mol. The ΔH_цепь contribution is provided by hydrogen bonding in the protein interior (90% of all internal polar groups of which form Hydrogen Bonds [17]) and by Structure/103.html">Van der Waals interactions. The resulting value of ∆G_общ = ∆H_цепь — ∆TS_цепь + ∆G_рacтв accounts for only a small fraction of the compensating terms, or approximately 10 kcal/mol.

This order of magnitude for the absolute value of ∆G_общ of the folding process has been determined experimentally for A large number of proteins containing about 150 residues [413]. To estimate ∆G_oбщ, researchers utilized hydrogen exchange rates in the N and R states [414–416], calorimetric data on chain unfolding, data derived from Denaturation curves (see review in [413]), as well as equilibrium constants K between the native and random Conformations found in immunological studies [418]. Because the value of ∆G_общ is small, any energy calculations aimed at establishing a correlation between the covalent and geometric structures of a protein must be exceptionally precise to yield meaningful results. Since non-covalent bonding forces in proteins are not yet fully understood, achieving such precision remains difficult (Ch. 3). It should also be noted that the Equilibrium Constant is extremely sensitive to Temperature changes.