Non-covalent interactions
A hydrogen bond (H-bond), is a specific type of interaction that involves dipole-dipole attraction between a partially positive hydrogen atom and a highly electronegative, partially negative oxygen, nitrogen, sulfur, or fluorine atom (not covalently bound to said hydrogen atom). It is not a covalent bond, but instead is classified as a strong non-covalent interaction. It is responsible for why water is a liquid at room temperature and not a gas (given water's low molecular weight). Most commonly, the strength of hydrogen bonds lies between 0 - 4 kcal/mol, but can sometimes be as strong as 40 kcal/mol In solvents such as chloroform or carbontetrachloride one observes e.g. for the interaction between amides additive values of about 5 kJ/mol. According to L. Pauling the strength of a hydrogen bond is essentially determined by the electrostatic charges. Measurements of thousands complexes in chloroform or carbontetrachloride have led to additive free energy increments for all kind of donor-acceptor combinations.
Hydrogen bond
The role of hydrogen bonds in protein folding has also been linked to osmolyte-induced protein stabilization. Protective osmolytes, such as trehalose and sorbitol, shift the protein folding equilibrium toward the folded state, in a concentration dependent manner. While the prevalent explanation for osmolyte action relies on excluded volume effects that are entropic in nature, recent circular dichroism (CD) experiments have shown osmolyte to act through an enthalpic effect. The molecular mechanism for their role in protein stabilization is still not well established, though several mechanisms have been proposed. Recently, computer molecular dynamics simulations suggested that osmolytes stabilize proteins by modifying the hydrogen bonds in the protein hydration layer.