Roundtable Review

Form for Function: How Pauling’s 1954 Nobel Revolutionised the Investigator’s Toolkit
Posted 12 July '13

PaulingThe start to the 20th Century was an exciting time to be living in. Despite the fact that wars between nations were being planned out and implemented: it did not stop the flow of creativity. The people of that generation were determined to move the world forward. And just like in Arts, Science was pushing boundaries with new ideas and discoveries. Part of this fruitful, scientific drive was paving the way for particle physics and molecular biology disciplines to enter the world of science; contrasting subjects that both concentrate on studying the behaviour of molecules. And the individual that was at the forefront of carrying this molecular ideology forward was Linus Pauling. His impactful work on understanding the nature of chemical bonding allowed him to be awarded with the Nobel Prize in Chemistry in 1954. Matter is defined by its structure and structure was what enticed Linus Pauling. In pursuit, it led him to discover the physical and chemical nature of how molecules bond together to put together a structure. In his words: ‘To understand the human body, we must know its structure. To understand cells we must know the structure of molecules. To understand molecules, we must know the structure of atoms and to understand atoms (which is what the physicists are doing), we must understand the structure of nuclei; the protons, neutrons and the electrons’. Not winning just one, but two (latter being a Nobel Peace Prize); Linus Pauling helped shape much of the molecular science that we now know and use.

Chemical Bonding in Nature.

What made his discovery of chemical bonding so significant? Bonding in essence is the fundamental physical phenomenon that keeps everything in place and resultantly gives matter their structure. From molecules to proteins to cells to the living body, chemical bonds hold things in shape and allow them to perform their function. Chemical bonding can be broken down into two categories: covalent and non-covalent bonding. The former is the result of atoms reacting together and sharing electrons, making permanent bonds.  Peptide covalent bond and phospho-diester covalent bond that give proteins and genetic (DNA and RNA) polymers their structure respectively are prime biological examples of this type of chemical bonding. Non-covalent bonding on the other hand is a non-permanent bonding event that occurs due to the constant movement of electrons in atoms. They can be intra-atomic and inter-atomic which contribute to structuring molecules like proteins and affecting their overall function. The strength of covalent bonding allows molecules to become resistant and retain their architecture. Non-covalent bonding allows them to become dynamic. Take a water molecule as an example. A simple covalent bond between two hydrogen atoms and one oxygen atom gives rise to a water molecule. But what makes a water molecule a dynamic entity is its ability to incorporate non-covalent bonding in the form of hydrogen bonding. Hydrogen bonding involves interaction between a partially (positively) charged hydrogen and a partially (negatively) charged oxygen. This allows a water molecule to diversify into structured ice crystals, loose liquid form and a liberated, gaseous form – with increasing environmental temperature. Other biological molecules such as proteins also rely on the temporary nature of non-covalent bonding to perform their function and be dynamic. Hence, Pauling’s groundbreaking discovery on the nature of chemical bonding has been the basis of much of our understanding of molecular biology today. It was this discovery that essentially gave birth to the field of Structural Biology as well.

The beginning of a new discipline: Structural Biology.

In 1922, Pauling first made use of X-ray Crystallography in the hope of deciphering what molecules look like in nature. Molecules are not visible to a naked eye due to the limiting resolution of optical vision and by making use of physical theories and intricate mathematics; Pauling worked towards devising ways to look at molecules at a microscopic scale. X-Ray Crystallography allows determination of the atomic structure of molecules by firing X-Rays onto a crystallised molecule under study (i.e. proteins). From the diffraction pattern attained, the distance between individual atoms and the atomic orientation and organisation in molecules can then be deduced. Most of the protein structures solved and found in the protein database are as a result of protein crystallography work till date. During the process of developing crystallography, Pauling took a step further and incorporated quantum mechanics to present the basis of studying molecules. He first studied the structure of a glycine molecule, the simplest amino acid in nature. Later, the advancement in crystallography and Pauling’s shift towards studying biological molecules, led to a series of papers published in 1951 that first described the molecular nature of proteins. It was the time when we first got our introduction to what proteins look like in three dimensions: From its primary (polypeptide chains), secondary structure (alpha helical and beta sheets) orientations to the full 3D structure. Although a chemist by background, Linus embraced the very notion of understanding our world through all disciplines of science. His participation in understanding the molecular nature of biology helped advance molecular and structural biology.

Applications of this discovery.

Since the departure from the discovery of chemical bonding to studying biological molecules, the application and significance of knowing the nature of bonding have been vast. Structural biology has come a long way since its nascent, early days, as it now incorporates a combination of biophysical methods to tease apart and study molecules in biology. From simple protein molecules to large macromolecules, we are slowly deciphering the structural diversity observed in biology. And this gradual uncovering of the veil over molecular biology is helping efforts to treat diseases fatal to human health. Much of the pharmaceutical and biotechnological efforts are presently focused on using Structural Biology and Computational Biology to understand how molecules behave in the early efforts of devising novel agents in therapeutics. Drug design requires understanding how a drug molecule interacts (through chemical bonding) with its target, protein molecule. Consequently, knowing the structure of both entities and the nature of chemical bonding helps drive the early stages of drug discovery. This is just one glimpse of applying the basis of molecular bonding knowledge in science today. Being the core of molecular biology, the knowledge of chemical bonding in molecules is driving most of biological research today. And we have Linus Pauling to thank this for.

About Login
Oxbridge Roundtable Ltd © 2015. All Rights Reserved.