Relationship between intramolecular hydrogen bonding and solvent accessibility of side-chain donors and acceptors in proteins.

This study shows that intramolecular hydrogen bonding in proteins depends on the accessibility of donors and acceptors to water molecules. The frequency of occurrence of H-bonded side chains in proteins is inversely proportional to the solvent accessibility of their donors and acceptors. Estimates of the notional free energy of hydrogen bonding suggest that intramolecular hydrogen-bonding interactions of buried and half-buried donors and acceptors can contribute favorably to the stability of a protein, whereas those of solvent-exposed polar atoms become less favorable or unfavorable.