Covalent bonds are responsible for peptide chains forming and linkage. Other secondary bonds with much weaker interactions are involved in the complex three-dimensional structure of proteins.
Covalent Peptide Bonds
It’s a covalent chemical bond formed between two amino acids. This occurs when an amino group loses a hydrogen atom and a carboxyl group loses a hydroxyl group, resulting in the release of a water molecule. The primary structure of proteins is constructed by it. Resonance allows all the atoms of peptide bond to lie in a same plane. Boiling water doesn’t break this very strong interaction. Only enzymes, acids, or bases can break it. Refer to previous articles to get more details about peptide bonds or polypeptides.
Disulfide Bond is a weaker covalent bond.
It joins two sulfhydryl groups in cysteine. Its bond energy is only about 60% of a peptide bond, but it’s still much stronger than interactions. It’s involved in the correct folding of proteins. Hydrophobic amino acids sometimes surround disulfide bonds to form local hydrophobic centers to prevent water molecules from entering protein. They occur both intramolecularly and intermolecularly. An insulin molecule consists of two peptide chains, A and B. The A chain has one internal disulfide bond that bends it. The A and B chains are also linked by two disulfide bonds.
It is dynamic. Although it can be broken by reducing agents, it also regenerate with the help of oxidizing agents. When it breaks or regenerates, the structural changes cause protein to lose its biological function. Sometimes these conformational changes will enhance biological activity or result in new functions. Thus, this dynamic property can regulate life activities with the help of glutathione.
Salt Bridge
Salt bridges are electrostatic interactions between amino acid side chains with opposite charges. For example, positively charged Arg and negatively charged Asp will attract to build salt bonds. Its stability is subject to pH and salt concentration. If salt concentration is very high, some charged R groups will combine with salt ions. Similarly, too acidic or too basic solution will neutralize some charged R groups, hindering salt bridge formation. Although its strength and stability aren’t as good as covalent bonds, it’s stronger than hydrogen bonds. Therefore, it still plays a crucial role in maintaining protein structure.
Hydrogen Bond
Hydrogen bonds in proteins come from peptide bonds and side chain groups. Partially positively charged hydrogen atoms and partially negatively charged oxygen atoms attract each other. Peptide bonds are very common in proteins, so it result in some repetitive structures such as α-helices and β-sheets. In an α-helix, carbonyl oxygen in nth residue forms a hydrogen bond with amide proton in (n+3)th residue. Hydrogen bonds in β-sheets span different peptide chains or different regions of the same peptide chain. They provide great mechanical strength for fibrous proteins, such as triple helix in collagen andβ-sheets and α-helices in spider silk.
Polar groups in side chains, such as hydroxyl, amide, and sulfhydryl groups, can also form hydrogen bonds. Although their uneven distribution can’t form regular structures, hydrogen bonds from side chains are very important for the tertiary structure. They span great distances to connect amino acids in different regions to maintain their complex spatial structure.
Hydrogen bonds are easier to break or rebuild than salt bridges. The reason is that they will combine with other charged ions in solution. This dynamic property allows proteins to adjust their structure that is relative to biological activity when environment changes. Additionally, intense collisions due to high temperatures will also break down them. Despite this, they’re still the most important secondary interaction since the large quantity. People even calculate the binding strength of hydrogen bonds to infer whether a protein and a ligand is matched, especially in drug development.
Hydrophobic Interaction
Hydrophilic groups are located on the surface to touch with water. Water molecules arrange into a regular clathrate structure around hydrophobic substances. Hydrophobic groups tend to concentrate inside globular proteins to avoid water. However, electrical attraction disrupts clathrate structure to makes water molecules arrange in a more chaotic way. Maintaining an orderly structure requires more free energy, so hydrophobic substances tend to cluster to reduce the area in contact with water. A smaller clathrate structure surrounding them means lower free energy.
Hydrophobic groups tend to concentrate inside the globular proteins to avoid water, while hydrophilic groups are located on the surface to contact with water by hydrogen bonds. Why is this so? Water molecules arrange into a regular clathrate structure around hydrophobic substances. However, the electrostatic attraction between water and hydrophilic groups disrupts clathrate structure to make more disordered arrangement. Maintaining an orderly structure requires more free energy. Therefore, the hydrophilic parts expose themselves to aqueous medium to create disorder. If the hydrophobic parts also have to coexist with water, the minimal order is achieve by clustering together to reduce volume-to-surface ratio.
Van der Waals Forces
They are weak attractive forces between atoms or molecules that are close to each other. Although they are much weaker than interactions mentioned above, they influence the boiling point, melting point, viscosity of organic substances. The tertiary and quaternary structures of biological macromolecules like proteins and DNA are also constructed by these forces.
Dipole-Dipole interactions are found between polar molecules with permanent dipole moments. It’s similar to the situation that two small balls with opposite charges attract each other. Another situation is Dipole-Induced Dipole Forces.
You can imagine a scene like this: a charged glass rod will attract a small piece of paper because rod will induce an electric charge on the paper.
London dispersion forces are the weakest type of Van der Waals forces. The electron cloud within an atom forms a temporary dipole at a certain moment, which induces charges in surrounding particles. London Dispersion Forces exist in all atoms and molecules.