Hydrogen Bonds in Proteins: Role and Strength

Abstract Hydrogen bonds provide most of the directional interactions that underpin protein folding, protein structure and molecular recognition. The core of most protein structures is composed of secondary structures such as α helix and β sheet. This satisfies the hydrogen‐bonding potential between main chain carbonyl oxygen and amide nitrogen buried in the hydrophobic core of the protein. Hydrogen bonding between a protein and its ligands (protein, nucleic acid, substrate, effector or inhibitor) provides a directionality and specificity of interaction that is a fundamental aspect of molecular recognition. The energetics and kinetics of hydrogen bonding therefore need to be optimal to allow the rapid sampling and kinetics of folding, conferring stability to the protein structure and providing the specificity required for selective macromolecular interactions. Key concepts: A hydrogen bond is formed by the interaction of a hydrogen atom that is covalently bonded to an electronegative atom (donor) with another electronegative atom (acceptor). Hydrogen bonding confers rigidity to the protein structure and specificity to intermolecular interactions. The accepted (and most frequently observed) geometry for a hydrogen bond is a distance of less than 2.5 Å (1.9 Å) between hydrogen and the acceptor and a donor‐hydrogen‐acceptor angle of between 90° and 180° (160°). During protein folding, the burial of hydrophobic side‐chains requires intramolecular hydrogen bonds to be formed between the main chain polar groups. The most stable conformations of polypeptide chains that maximize intrachain hydrogen‐bonding potential are α helices and β sheets. Specificity in molecular recognition is driven by the interaction of complementary hydrogen‐bonding groups on interacting surfaces.