Structure Drives Function | Protein Biochemistry and Biology

One of my favorite key concepts that defines biology is that:

Structure Drives Function

For example, protein structure influences protein function.  Proteins are the main biochemical macromolecules that dictate various functions in each organism.  That is also why understanding proteins can help people understand a lot about biology.  Similarly, anatomical structure determines anatomical function.  For example, understanding what the liver and various sections of the liver look like helps to understand its role in metabolism.

In other words, once you know a protein’s structure, you will glean a greater understanding of its function.  Once you know its function, you can better understand biological systems.  One application of knowing its structure and function, is that you can use structure-based design to rationally design inhibitors to selectively inhibit various proteins, or various sections within a protein.  This is a much better approach to designing drugs than randomly guessing which inhibitors can inhibit which proteins, which can incidentally also result in many side effects due to nonspecific binding to other proteins which you are not intending to target.  An example of a recent drug that was designed through the rational structure-based drug design approach was the neuraminidase inhibitor against influenza.  Examples of neuraminidase inhibitors are Tamiflu and Relenza. The following is a ribbon representation of the neuraminidase protein, in complex with an inhibitor:

influenza neuraminidase in complex with inhibitor

The current major problem is that the protein sequence, although known for almost all proteins since the known DNA gene sequence can be converted to the corresponding protein sequence, is unable to predict protein structure theoretically.  There have been many recent advances in being able to experimentally solve high-resolution protein structures through X-ray crystallography and nuclear magnetic resonance (NMR).  However, many of these experiments to try to determine protein structures are long, tedious, and have uncertain outcomes in many instances.  Growing crystals on Earth that are suitable for X-ray diffraction, for example, is extremely difficult. There are many different attempts currently being approached to address this protein structure problem in a more theoretical fashion through computers and bioinformatics.  For example, the Folding at Home project tries to predict how proteins fold into its three-dimensional shape by using many computers distributed across the globe. People with computers can help with this distributed computing project by running programs in the background of their computers. There are also software and programs that try to model protein structures of proteins that are similar in sequence to those of existing known protein structures. An example is SWISS-MODEL from Expasy

The future holds much promise for biology and combatting various diseases through rationally targeting selective proteins through protein structure prediction and structure-based drug design.

If you liked this article, please subscribe to future articles on Thought Flashes through one of the subscription options on the rightmost column near the top.