Force in Protein Folding

In sections 7.14 and 8.7.6 we discussed the average force operating on a particle that originates from the presence of the solvent. We generalized this concept for a solution containing a single macromolecule. 

consider a macroscopic process, e.g., expansion of A molecules in an ideal-gas phase from volume ViolV. In this process AG 0 and we say that there is a thermodynamic force driving the system from the initial state i to the final state /. 

If the system is macroscopically large, then once we reach the equilibrium state, the thermodynamic force becomes zero. We know also that even at equilibrium there are always fluctuations around the final state. For very large N, these fluctuations are relatively small, and are usually ignored in thermodynamics. 

If N is small, then repeating the same experiment as above, we shall again find that the system approaches an equilibrium state, but now the fluctuations about the equilibrium state are relatively large. As an extreme case of a small system, let Ri and R2 be the positions of two spherical solutes in a solvent. The potential of average force between the two solute particles looks like the curve in Fig. 8.23. Suppose that we could move the two solutes along the line connecting their center. The entire system includes both 

FIGURE 8.23. A schematic form of the potential of average force between two solutes. The two solutes at R will initially move away from each other. In spite of the thermodynamic force towards R.  

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K. A. Dill, Biochemistry, 29, 7133 (1990). Dominant Forces in Protein Folding. 

T. Determining the role of hydrahon forces in protein folding. J. 47. Phys. Chem. B 1999 103 5413-5426. 

K. A. Dill, Dominant Forces in Protein Folding, Biochemistry, 29, (1990) 7133 K. A. Dill, Theory of the Folding and Stability of Globular Proteins, Biochemistry, 24 (1985) 1501. 

J. Clarke and P.M. Williams (2005). Unfolding induced by mechanical force. In Protein Folding Handbook. Part /, Edited by Buchner, J. and Kiefhaber, T. Wiley-VCH New York. 

This was in 1980. Since then I became convinced that Kauzmann s model, based on transferring a solute from water into an organic liquid, is inadequate for estimating the contributions of H0O groups to the overall driving forces in protein folding and protein-protein association. In these processes it is... 

Bolen, D. W. and I. V. Baskakov. 2001. The osmophobic effect Natural selection of a thermodynamic force in protein folding. Journal of Molecular Biology. 310, 955. 

Ben-Naim, A. (1994) Hydrophobic-Hydrophilic Forces in Protein Folding. In Structure and Reactivity in Aqueous Solutions, C. J. Cramer and D. G. Thrular, Ed. American Chemical Society Washington, D.C., Vol. 568 pp 371-380. 

The major driving force in protein folding is the hydrophobic effect. This is the tendency for hydrophobic molecules to isolate themselves from contact with water. As a consequence during protein folding the hydrophobic side chains become buried in the interior of the protein. The exact physical explanation of the behavior of hydrophobic molecules in water is complex and can best be described... 

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