Here is a link to an article I was invited to write by my good old friend, Dr. Eddie López-Honorato from CINVESTAV – Saltillo; Mexico, for the latest issue of the journal ‘Ciencia y Desarrollo’ (Science and Development) to which he was a guest editor. ‘Ciencia y Desarrollo’ is a popular science magazine edited by the National Council for Science and Technology (CONACyT) of which I’ve blogged before.
This magazine is intended for people interested in science with a general knowledge of it but not necessarily specialized in any field. With that in mind, I decided to write about the power of computational chemistry in predicting some phenomena while shedding light in certain aspects of chemistry that are not that readily available through experiments. The article is titled ‘Chemistry without flasks: Simulating chemical reactions‘. The link will take you to the magazine’s website which is in Spanish, as is the article itself, and only to the first page; so, below I translated the piece for anyone who could be interested in reading it (Hope I’m not infringing any copyright laws!). Don’t forget to also check out Dr. López-Honorato’s blog on nuclear energy research and the development of materials for nuclear waste containment! Encourage him to blog more often by liking and following his blog.
Chemistry without flasks?
Typically we think of a chemist as a scientist who, dressed in a white robe and protected with safety glasses and latex gloves, busily working within a laboratory, surrounded by measurement equipment, glassware and bottles with colored substances; pours one substance onto other substance, transforming them into new substances while noting that the chemical reaction occurs through color changes, heat release , perhaps gas, and occasionally even an explosion.
Thus chemistry, the study of the material processing involves active experimentation to accomplish chemical reactions subsequently confirmed, although indirectly, that the changes have been conducted in the microscopic world, moreover, in the molecular and atomic world. The chemist plans these changes based on the knowledge he has of the chemical properties of the substances of which he started and, like any other substance, are due to its molecular structure, i.e., the spatial arrangement of the atoms that form it.
Under this archetypal image just posed, then it’s at least funny to think that there is a branch of chemistry named Theoretical Chemistry.
What is theoretical chemistry?
Theoretical chemistry is a kind of bridge between chemistry and physics; using laws and equations that govern the subatomic world, to calculate the molecular structure of a substance, more specifically calculate the distribution of electrons surrounding the molecule forming a cloud, which interact with the electron cloud of another molecule to form a new substance. It is based on the knowledge of the electron density cloud or we can understand and predict the chemical properties of any substance. We can then define theoretical chemistry as the set of physical theories that describe the distribution and properties of the electron cloud belonging to a molecule, in this particular mathematical description we call electronic structure and this is the starting point for descriptions and chemical predictions.
What is it good for?
Through theoretical chemistry we can find answers to fundamental questions about the structure of matter. Consider a molecule of water, which has the chemical formula H2O. This formula implies that there are two hydrogen atoms attached to an oxygen atom But what spacial structure does a water molecule have? The simplest geometry it could take would be a linear structure, in which the angle formed by the three atoms is 180 °. However, the water molecule has an angle of 109 °, far from a linear structure. In Figure 2 we can see the result of the calculation of the electronic structure of H2O, it observed that the electron cloud that exists on the oxygen atom also has a place in space and thus push the hydrogen atoms bringing them together instead of allowing them to take a more comfortable conformation.
Figure 2. Oxygen remaining electrons (red cloud around the oxygen atom) that are not chemically push the hydrogen atoms towards each other.
The industrial area currently impacted by the application of theoretical chemistry is the pharmacist, as they generate a new drug involves significant investment in financial and human resources, so predicting the properties of a molecule with pharmacological activity before synthesizing is highly attractive. Therefore it has been generated within the theoretical chemistry field, otherwise known as branch Rational Drug Design.
Drugs acting on our organism when active molecules interact directly with the various proteins which are distributed in the tissue cells. If the structure of the protein is known and we attack is known also a drug which acts on it, then we can design similar drugs having greater efficacy in the treatment of diseases. But it is not only fit one molecule to another, but to calculate the energy of interaction, the energy of dissolution and the probability that this interaction can be observed experimentally (Figure 3). The calculation of the interaction energy between the drug and the protein tells how strongly attract each other, a weak attraction drug will result in a low efficiency, while a greater attraction involve a more effective drug.
How do you calculate a molecule?
All matter exists in the universe is made of atoms, which in turn are composed of a nucleus of protons and neutrons surrounded by a cloud of electrons. When two or more atoms combine to form a molecule combining do their electron clouds and how do these combinations are best described by the equations of quantum mechanics, the branch of physics that describes the behavior of the subatomic world. However, due to its complexity, the equations of quantum mechanics can only be accurately resolved in the simplest cases such as the hydrogen atom, which consists of a single electron orbiting a proton. We must therefore resort to a range of methods and approaches to tackle cases of chemical interest and even biological.
For years the only available computers could solve the approximate equations for small molecules, no later than thirty atoms, which which can be interesting, but not entirely useful. Today modern supercomputing equipment (which may amount to up to tens or even hundreds of powerful computers connected together to work cooperatively) allow us to make models with hundreds of atoms molecules such as proteins or DNA fragments.
While the software available to perform these calculations is developed continuously for the last thirty years has been the progress in the design of computer systems able to perform thousands of operations per second the cornerstone that has made the theoretical chemistry a predictive tool commonly used. Today the branch known as Molecular Dynamics, which studies the interactions between molecules over time, has benefited from the development of the latest game consoles, as their processors, known as graphics processing units (GPUs , for its acronym in English) are able to perform calculations in parallel: Many of the images seen in our video games are actually calculated, not animated, this means that the console must calculate how to answer each item on the screen According to each stimulus we introduce. Conversely, if the images were animated, the answers would be always the same and the game would become unrealistic. Each game event should be calculated almost immediately to maintain its fluidity and emotion, in such a way that these GPUs have to be able to perform several mathematical operations simultaneously.
Traditionally molecular dynamics is based on the equations of classical physics, which only see the time evolution of molecules like solid objects collide, hundreds of molecules floating in water or other solvent. With the advent of GPUs can include dynamic calculating the electronic structure so we can peek into biological processes such as DNA replication or the passage of nutrients through a channel protein embedded in the membrane of a cell.
Since the fundamental understanding of the distribution of electrons in a molecule, its structure and properties to rational drug design, new materials based on molecular modeling theoretical chemistry is a powerful tool which is constantly progressing. The development of computer systems increasingly powerful detail allows us to meet the electronic processes involved in a chemical reaction while we can predict the real-time progress of molecular transformations. All this brings us ever closer to the dream of modern alchemists: transform matter to obtain substances with properties designed to pleasure.
In the nineteenth century, the American philosopher Ralph Waldo Emerson, wrote: “Chemistry was born from the dream of the alchemists to turn cheap metals into gold. By failing to do so, they have accomplished much more important things. ” And yes. Today we delve into the innermost secrets of nature not only to understand how it works but also to modify its operation on our behalf.
Last spring I was invited by The State Council for Science and Technology (COMECyT) to be part of the jury in the 5th Mexican Science and Engineering Fair and now we just had the finals here in Toluca.
For the first part of this competition several projects were evaluated in their originality and relevance as well as their feasibility. The ones that were accepted were later on reevaluated in their progress and now for the actual fair, students from all across the state came to show their results. The scope of the projects I had to evaluate dealt with the use of natural resources indigenous to their local surroundings as starting materials with different applications.
Among the ones that were exhibited today there was a project dealing with substituting wood for cactus in agglomerates. This is a great idea considering the ubiquity of cactus in Mexico and the little attention that is paid to their logs. In another booth, some piezoelectric devices are being plugged together under a sort of mat which will be stepped on by pedestrians generating electricity from their weight, taking advantage thus of their kinetic energy. Once again, on cactae, another team wants to use the resin that comes out of the raw plant as a co-polymerizing agent. I could go on and on about the projects but please visit this link to learn more about it. Below, I share with you some pictures I took from the fair.
Today’s event was attended by the local scientific authorities and by the State Governor Dr. Eruviel Ávila, who in his speech talked about the importance of science and technology development not only in this but in all nation’s states.
Kudos to the local Council for Science and Technology for promoting these events and thanks for including me as part of them.
A couple of months ago, maybe a little bit more, I got the news that the project I submitted to the National Council for Science and Technology (CONACyT) was approved! Now we only have to wait for the money to actually show up and that might take a while – a long while! Nevertheless this is always very good news and we are very excited about it because this means more money for research, specifically on the electronic molecular pathways of photosynthesis.
When I submitted the project I wrote a little post about the funding scheme which seemed, if not unfair, at least flawed, and I still believe in what I wrote. To be honest I thought it wouldn’t be funded but it turns out it was but I still think the reviewing process could be better.
There is a lot of research to do – too little time to do it.
In science one thing is true and universal: We need funding. Here in Mexico the main source of funding comes from the National Council for Science and Technology (Consejo Nacional de Ciencia y Tecnología, CONACyT) which is an institution that depends directly from the federal government. Over the years different policies have prevailed and right now we are not looking into a good future. I wont go into all the alleged corruption or about the prevailing notion of favoritism within the institution’s scheme for funding research. I just want to write about the process of projects evaluation and what I think are its great shortcomings.
So first, as in any other part of the world, it all begins with a proposal being submitted for evaluation. In this particular case there is a specific application for “Young Researchers”, that is people who are newcomers to any scientific institution in the country, who are in need for a large amount of resources in order to get their own labs going. The notion of an “associate researcher” is not well understood, I think. After the submission is complete and the paperwork validated, the proposal is sent to a few other researchers in the field who either accept or decline to review the project and then are asked concise questions about the originality and relevance of the project; its feasibility; the proponent’s profile about how well suited he or she is to deliver what is being promised, and finally they are asked to evaluate how well justified is the requested budget. The reviewers then turn their comments, and rankings, to CONACyT in which a committee gathers all the data and ranks all the projects. Those projects with the higher ranking get their funding with, maybe, minor adjustments in order to stretch the reach of funding to as many projects as possible. Some other criteria are used, for example researchers at institutions with small budgets have increased chances of being funded than those on a large institution. It is a matter of balance: giving the money to those who need it but that at the same time will sure do more (and better) with it.
So far it all sounds pretty good and fair to me! except there is a problem: Reviewers don’t always do their job properly and sometimes you get to read comments such as
the proponent has no experience in graduating students
well, thats why I clicked the “Young Researcher” button. Some other pearls of wisdom include
the proponent didn’t take into consideration the latest publications in the field he is trying to study
and then he/she enlists references with publication dates posterior to the date of the proposal’s submission! Sometimes our proposals may not be thoroughly well read (or, lets admit, written) and reviewers give you a bad review for omitting things that you indeed covered. But once you get a bad review (from an anonymous peer) there is no turning around, you only find out what they wrote once you have been declined the grant.
My little suggestion: Let the review process be questioned, just once per reviewer and without the possibility of modifying the proposal. That is, once a reviewer emits his or her comments then I could get to read them and address their concerns in a single letter. If I can prove them something so evident as a conflicting set of dates between missing references and the proposal submission’s, then they would have to change their ranking, but without giving me the chance to modify the project anymore as to fit their comments. The process would take longer, maybe, but it already takes more than half a year! a few more months could be worthy if a more fair ranking is obtained.
Science needs funding; not all the scientific proposals deserve funding, true.