Molecular Biology: Protein Structure and Function - Stepanov V.M. 2005

Secondary Structure
The Role of Hydrogen Bonds in the Formation of Secondary Structure

So far, when discussing Secondary Structure, we have considered a simplified model of amino acid residue behavior in the peptide chain, focusing primarily on steric constraints imposed by immediate neighbors. The next step, which complicates the picture while bringing it closer to reality, is accounting for non-covalent interactions between adjacent residues within a periodic secondary structure. At this stage, we still Abstract away THE CONTRIBUTION OF side chains and neglect long-range interactions with other PARTS OF THE molecule.

The main chain of a polypeptide contains only one periodically repeating element capable of forming Hydrogen Bonds: the peptide group, which can act as both a donor and an acceptor.

Just how significant is the stabilization of secondary structure by hydrogen bonding? To answer this question, we must consider a factor that has not yet been addressed: The Effect of the protein's aqueous environment. Water is an exceptionally strong competitor in hydrogen bonding, as it can function effectively as both a donor and an acceptor:

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It is to be expected that METABOLISM/18.html">The Influence of water will diminish as a compact 3D Cell/13.html">Protein Structure forms, the content of peptide bonds increases, and the probability of their interaction with one another rises. Indeed, studies of the simplest model system, N-methylacetamide (СН₃—СО—NH—СН₃), have shown that at low concentrations, The formation of dimers, such as

via intermolecular hydrogen bonds is virtually nonexistent. Only at very high N-methylacetamide concentrations (up to 10 M) does it dimerize almost completely. In the absence of water, for instance in carbon tetrachloride, complete dimerization is achieved at an amide concentration of just 0.2 M.

Both effects are at play in Proteins: peptide groups are brought into close proximity within the folded chain, making the probability of their encounter roughly equivalent to that in a 9 M N-methylacetamide solution. Of course, it is also crucial that the close approach of peptide bonds in a protein occurs not randomly, as in a concentrated amide solution, but within a cooperative system. At the same time, the polarity of the microenvironment surrounding the peptide bond in a compact protein globule is significantly lower than in water. The combination of these two factors makes hydrogen bonding between peptide groups a critically important structure-forming force.

Thus, the stability of secondary structure heavily depends on its incorporation into the compact Tertiary Structure of a protein. Conversely, due to their smaller size, Peptides lack the necessary stability to maintain a rigid secondary structure on their own. For example, even a relatively long natural peptide like Glucagon, which consists of 29 amino acid residues, exists in solution as an equilibrium mixture of conformers; it adopts an α-Helix only upon forming a complex with its receptor protein—that is, when incorporated into a compact structure through non-covalent interactions.