Transferring the experiments to the computerized space - a popular explanation of the science of the 2013 Nobel laureates in chemistry

Chemists all over the world plan and carry out experiments with the help of their computers every day. Thanks to the help of the methods developed in the 2013s by the three researchers who won the XNUMX Nobel Prize in Chemistry, Martin Karpelos, Michael Levitt and Arie Werschel, they manage to examine each and every step in complex chemical processes hidden from view

Chemical reactions occur at the speed of light; Electrons skip between the nuclei of atoms, hidden far away from the expectant, longing eyes of the scientists. The winners of the 2013 Nobel Prize in Chemistry made it possible to map the mysterious ways of chemistry with the help of computers. Detailed knowledge of chemical processes allows to improve and optimize chemical catalysts, drugs and solar cells.

Chemists all over the world plan and carry out experiments with the help of their computers every day. Thanks to the help of the methods developed in the XNUMXs by the three researchers Martin Karpelos, Michael Levitt and Arie Warschel, they succeed in examining each and every step in complex chemical processes hidden from the naked eye.

In order for you, the reader, to understand how humanity can benefit from the achievement of the three winning scholars, we must begin with an example. Put on your lab coat, because we have a challenge for you: create an artificial photosynthesis system. The chemical reaction that occurs in green leaves fills the atmosphere with oxygen and is one of the prerequisites for life on earth. However, the reaction is also interesting from an environmental point of view. If you succeed in imitating the mechanism of photosynthesis you will be able to develop more efficient solar cells. When a water molecule is split, oxygen is created, but at the same time, hydrogen is also created that can be used to power vehicles. So there is a very good reason to initiate such a venture. If you succeed in it, you will actually be able to contribute to solving the problem of the greenhouse gas effect.

More on the same topic on the science website:

• The work of the winners of the Nobel Prize in Chemistry, including Prof. Aryeh Warshel, is closely related to the Weizmann Institute
• Prof. Aryeh Warshel, a graduate of the Technion and the Weizmann Institute and currently in California, and Prof. Michael Levitt, a visiting researcher at the institute, won the Nobel Prize in Chemistry together with Martin Karpelos

A picture says more than a thousand words - but not everything

As a first step in this project, you will probably turn to the Internet and look for a XNUMXD image of the proteins responsible for the photosynthesis mechanism. These images are freely available in extensive databases on the Internet. On your own computer you can twist and rotate the image as much as you want. The detailed image will reveal to you huge protein molecules consisting of tens of thousands of atoms. Somewhere in the center of the image you will find the small area known as the 'reaction center'. At this point the water molecules undergo fission. However, only a small number of atoms are directly involved in the reaction. Among other details, you will be able to identify four manganese ions, one calcium ion and several oxygen atoms. The image clearly shows where the different atoms and ions are located relative to each other, but the image will not tell us anything and a half about the roles of these components. This is the question you must solve in a research way. Somehow, electrons must move from the water molecule and combine with four protons to produce a hydrogen molecule. How exactly does this happen?

It is almost impossible to map the details of this complex process using normal chemistry methods. Countless events occur in the fraction of a millisecond - a common time scale in most types of experiments that take place in vitro. From the image on your computer it is also difficult to understand exactly how the process takes place, since the image itself was taken when the proteins were in a stationary and still state. However, when sunlight hits the green leaves, the proteins are filled with energy and the entire atomic structure changes. In order to understand the chemical reaction, you need to know exactly what this high-energy state looks like. It is precisely at this point that you summon the help of the computer programs whose foundation was laid by the three crying Nobel Laureates for 2013.

Theory and practice - a successful mutual fertilization mechanism
With this type of software you will be able to calculate a number of possible reaction pathways. This operation is called simulation or modeling. In this way, you will be able to get an idea of ​​the defined roles that the different atoms perform in the different stages of the chemical reaction. And when you have the computerized probable reaction pathway, it is easier to carry out practical experiments that can confirm or refute the results of the calculation. The results of these practical experiments, in turn, will be able to grow new clues that will lead to better simulations - the theory and the practice violate and promote each other. As a result, chemists today spend much more time in front of their computer screen than in the test tubes.

So, what is so special about the computer programs for which the 2013 Nobel Prize in Chemistry was awarded?

Combining the best of both worlds

In the past, when chemists wanted to simulate molecules on computers, they used programs that were based either on the laws of Newtonian physics or on the laws of quantum physics. Each of these types of software had strengths and weaknesses. The classical programs could calculate and process large chemical molecules. They could only show molecules in their stationary and still state, but at the same time they provided the chemists with a pretty good representation of the location of the various atoms in the molecules. However, these programs did not allow simulating chemical reactions. During the reaction, the molecules are charged with energy; They undergo energetic excitation. Classical physics fails to deal with such situations, hence its main limitation.

When chemists wanted to simulate chemical reactions, they had to turn to quantum physics; The dual theory states that electrons can exist simultaneously as both particles and waves. The strength of quantum physics lies in the fact that it is unbiased and the model does not depend on the views of the scientist. As a result, the computer simulations are much more realistic. The disadvantage is that these calculations require the use of enormous computing power. The computer is required to process the state of each and every electron and every nucleus found in the atoms of the molecule. This situation can be compared to the number of pixels in a digital image. A large amount of pixels will provide you with a high resolution, but at the same time it will require you to use greater computing resources. Similarly, calculations based on quantum physics allow obtaining detailed information of chemical processes, but they require the use of large computing power. In the XNUMXs, this limitation meant that scientists could only perform calculations on small molecules. In these calculations, the scientists also had to ignore the interactions of the molecules with their environment, even though chemical reactions in real life often occur in a solution of some kind. Thus, if scientists wanted their calculations to also include solvent effects on the reaction, they had to wait decades for the results.

Thus, classical chemistry and quantum chemistry were inherently different, and in some respects even opposed to each other. However, the winners of the Nobel Prize in Chemistry for 2013 managed to create a bridge between these two worlds of chemistry. In their computer models, Newton's laws and his apple collaborated with Schrödinger and his cat.

Quantum chemistry cooperates with classical chemistry

The first step towards this collaboration took place in the early seventies in the laboratory of Martin Karpelos at Harvard University in the USA. Karpelos was firmly planted in the quantum world. His research group developed computer programs that were able to simulate chemical reactions with the help of principles from quantum chemistry. In addition, he developed the 'Kerpelos equation' (from Wikipedia) used in nuclear magnetic resonance (NMR); A well-known method among chemists that relies on the quantum chemical properties of molecules. Upon completion of his doctoral research at the Weizmann Institute of Science in Rehovot, Israel, Aryeh Warshel arrived at Karpelos' laboratory in 1970. The institute had a powerful computer called 'Golem' after a well-known figure in Jewish folklore. Using this computer, Aryeh Varschel and Michael Levitt developed a breakthrough computer program based on the classical theories. The software enabled the modeling of all types of molecules, even large biological molecules.

When Aryeh Warshel joined Martin Karpelos at Harvard, he brought with him the computer software he had developed at the Weizmann Institute. From this starting point, they developed together a new type of software that performed different types of calculations on different electrons. In most molecules each electron orbits around a defined atomic nucleus. However, in some molecules, certain electrons can move around several atomic nuclei. This type of 'free electrons' can be found, for example, in the retinal molecule, which is a molecule anchored in the retina of the eye. Karpelos has long expressed a great interest in retinal since the chemical-quantum properties of this molecule affect biological functions; When light hits the retina, the free electrons in the retinal molecule absorb additional energy which results in a change in the structure of the molecule. This is the first stage of human vision.

At the end of many efforts, Karpelos and Worschel succeeded in modeling the retinal molecule. At the same time, they began their research with similar molecules with a simpler structure. They developed a computer program that relies on quantum physics to calculate the state of the free electrons, while applying simpler classical theories for all the other electrons and all the nuclei of the atoms in the molecule. In 1972 they published the findings of this study. It was the first time that any researcher was able to bring about a chemical collaboration between classical physics and quantum physics. Although the software was groundbreaking, it also had one limitation - it could only handle molecules with mirror symmetry.

Universal software for calculating the chemistry of life

After two years at Harvard University, Arie Warschel reunited with Michael Levitt. Levitt had just completed his doctoral research at the University of Cambridge in Great Britain, which at the time was the world leader in the study of biological molecules such as DNA, RNA and proteins. He used his classic computer program to gain a better understanding of the structures of biological molecules. The limitations remain, mainly the possibility of examining molecules in their quiescent state.

Levitt and Worschel aspired to greatness - they wanted to develop software that could be used in the study of enzymes, which are proteins that control and promote chemical reactions in living things. As a young student, Varschel became interested in the activity of enzymes. It is the cooperation and interrelationships between enzymes that enable the existence of life - they practically control all the chemical reactions in the living body. If you want to understand life - you must understand the activity of enzymes.

In order for the simulation of enzymatic reactions to be possible, Levitt and Worschel were required to make the cooperation between classical chemistry and quantum chemistry tighter. It took them several years to overcome all the setbacks they faced. They began their experiments at the Weizmann Institute in Rehovot, but when Levitt completed his doctoral studies several years later, he returned to Cambridge where he joined Worschel. In 1976 they achieved their goal and published the first computer model of an enzymatic reaction. Their software was revolutionary because it could be used past any type of molecule. The size of the molecule was no longer a limitation in the field of imaging chemical reactions.

Focus on the heart of the action

When chemists today model chemical processes, they apply computing power exactly where it is needed - they perform demanding physical-quantum calculations only on those electrons and atomic nuclei that directly affect the chemical process. This way, they get the highest resolution in the exact place where it matters. The rest of the molecules are modeled using classical equations. In order not to waste computing power, Michael Lott and Arie Warschel reduced the workload placed on the computer even more - the computer does not need to refer to every individual atom in areas that are not in the important parts of the molecule. They showed that several atoms can be merged during the calculations.

In the calculations made today, the scientists added a third layer of visualization - quite simply, the computer can, in those areas far from the chemical process, bundle together atoms and molecules and treat these aggregates as a homogeneous mass. In the scientific community this mechanism is defined as the dielectric medium.

The distance to which the effectiveness of simulations will reach depends on the future
The fact that scientists these days use computers to perform experiments has led to an even deeper understanding of the behavior of chemical processes. The power of the methods developed by Martin Karpelos, Michael Levitt and Arie Warschel lies in their universality. They can be used to study all types of chemistry; From molecules in the living world to chemical processes used in industry. Thanks to these methods, scientists can improve solar cells, chemical catalysts in car engines and even medicines.

At the same time, progress in this area will not stop here. In one of his publications, Michael Levitt described one of his dreams - to simulate a living organism at the molecular level. This is a tempting idea. The computer models developed by the three winners of the Nobel Prize in Chemistry for 2013 are extremely powerful tools. The scope of the applications and the human understanding and knowledge that these methods can advance remain in the hands of the future.