Protein stabilization energy is small
A typical protein contains a few salt-bridges, several hundred
hydrogen bonds and several thousand van der Waals interactions.
In spite of all these interactions proteins are only marginally stable.
Typical D G values for folding of proteins are in the range of -5 to
-15 kcal/mol i.e. not much greater than the energy of 2 or 3 hydrogen
bonds. This is because of several effects which cancel each other out.
The enthalpy change of protein folding (D H) is dominated by
hydrogen bonds. In the unfolded state the polar groups of the
protein will H-bond to solvent molecules and in the folded state
these polar groups will H-bond with each other. Hence the overall
enthalpy change on folding is small. The hydrophobic effect is thought
to make the largest contribution to D G. The hydrophobic effect
attributes the poor solubility of non-polar groups in water to the
ordering of the surrounding water molecules causing them to form