The importance of non-covalent

interactions in proteins:
Non-covalent interactions in proteins are of great importance as they are key to the formation,
structure and function of proteins. The most common non-covalent interactions in proteins are
van der Waals Forces, hydrophobic forces, hydrogen bonds and ionic bonds. Non-covalent
bonds are weaker than their covalent counterparts, with the energy released on formation
only 1-5 kcal/mol.[1] These weaker bonds allow for the formation of transient bonds, this is the
basis for many dynamic biological processes.

There is a significant biological importance to hydrophobic interactions in proteins.

Hydrophobic interactions cause an isolated protein to fold in on itself, reducing its
surface area and any unwanted interactions with the water molecules.[2] An example
of a protein which is folded in this way are tertiary proteins, here amino acids with
nonpolar R groups can cluster together inside the protein, leaving the hydrophilic
amino acids on the outside to interact with the surrounding water molecules.[3]

Hydrogen bonds form alpha helices and beta sheets in secondary proteins.
Hydrogen bonds form when there is an electrostatic attraction between a bonded
hydrogen atom and a more electronegative molecule in another.[4]
Hydrogen bonds help proteins retain structural integrity by conferring rigidity to the
protein structure. This type of bonding when applied to a protein and it’s ligands
gives the protein it’s directionality and it’s specificity. These are vital components to a
protein's ability to recognize other molecules.[5]
Non-covalent bonds were discovered in 1873 by Johannes van der Waals in order to
explain the observed differences between real and noble gases.
One of the first biochemists to understand how these non-covalent bonds interacted
in proteins was Walter Kauzmann. In 1959 Kauzmann discovered that the
hydrophobic effect plays an important role in the determining of the three-
dimensional shape of proteins.[6]
In the 1980’s hydrophobic interactions were researched with a greater depth through
statistical mechanical modelling. Researchers discovered that an important aspect of
protein folding was the hydrophobic interactions. This was due to how the the folded
protein’s sequence is disrupted both locally and non-locally, and this means that a
protein’s secondary structure equally a result of the tertiary structure as it is a cause
of it.[7]
It is of the utmost importance that we understand and continue to learn about the
non-covalent interactions in proteins for a multitude of reasons. For example, it is
imperative we continue to research this topic and apply our knowledge gained from
it. A deeper understanding is of relevance in the field of genomics and
pharmaceuticals due to both heavily relying on an understanding on protein structure
and function.[8]

From my research I have gained a lot of knowledge and insight into the importance
of non-covalent bonding in proteins such as it’s importance in the medical and
scientific fields. I have also learned about fascinating breakthroughs in the field using
AI based technologies. Google’s “DeepMind” AI lab has developed a system called
AlphaFold which is capable of predicting protein shape and structure when given an
amino acid chain.[9]

References:
[1] Harvey Lodish, Arnold Berk, S Lawrence Zipursky, Paul Matsudaira, David Baltimore,
and James Darnell., (2000), Molecular Cell Biology, 4th edition
[2]Anon, 2020. Hydrophobic Interactions. Available at:
https://chem.libretexts.org/@go/page/1506
[3]Abozenadah, H., Bishop, A., Bittner, S. and Flatt, P.M., (2018), Biochemistry- Defining Life
at the Molecular Level
[4] Alberts, Johnson, Raff, Roberts, Walter (1983), Molecular Biology of the Cell
[5] Roderick E Hubbard Muhammad Kamran Haider, (15 February 2010), Hydrogen Bonds
in Proteins: Role and Strength
[6] Walter Kauzmann,(1959), Some Factors in the Interpretation of Protein Denaturation,
Advances in Protein Chemistry
[7] Ken A. Dill,1,2 S. Banu Ozkan,3 M. Scott Shell,4 and Thomas R. Weikl The Protein
Folding Problem (2008)
[8] J M Yon, (2001), Protein folding: a perspective for biology, medicine and biotechnology
[9]Protein Structure Prediction Center, (2020), https://www.predictioncenter.org/casp14/