Tinkering with solvent helps to regulate the crystallization behavior of amino acids

During my PhD research, I investigated the possibility to influence the crystallization behavior of glycine by means of crystallization experiments under ambient conditions. I could show that it is possible to control the crystal formation of glycine from aqueous solution by isotopic exchange (H/D-exchange) on the solvent or the addition of mineral powder.

Glycine, the smallest amino acid, can crystallize from aqueous solution in different stable solid forms that are called α and γ polymorphs. I could show, on a statistical basis, that glycine forms the γ polymorph from heavy water (D2O) solutions instead of the α form, which is known to crystallize from normal water (H2O). Additionally, my studies regarding the introduction of inorganic powdered material, like fluorapatite (Ca5[F(PO4)3]) or calcite (CaCO3), into the crystallization system, also lead to γ formation. That is, our studies showed that the H/D exchange as well as the introduction of inorganic surfaces to the crystallization system influence and even regulate the crystallization behavior of glycine immensely.

The scheme illustrates that either deuteration of the molecule (top) or the application of biominerals (bottom) can lead to crystallization of γ-glycine (right) instead of α-glycine (left) from solution.

As methods the experimental grazing-incidence X-Ray diffraction (GIXRD) investigations accompanied by force field simulations were carried out to describe the interface between the amino acid solution and the biomineral surface structure. The support by computational methods offered an insight into the molecular interaction level and thereby provided nice approaches to explain the observed phenomena.

The video shows force field based molecular dynamic simulations regarding the dissolution of an interacting glycine dimer in aqueous environment of H2O and D2O molecules. Further, it shows the crystallization of glycine from a water solution droplet on fluorapatite (100) surface and calcite (101) surface.


Link to the PhD thesis of Anna Kupka: “Untersuchungen zur Steuerung des Kristallisationsverhaltens von Aminosäuren in Lösung durch den Einsatz von Deuterium oder Biomineralien”

Link to Graduate School Solvation Science

About the Author

anna_kupkaDr. Anna Kupka has recently accomplished her PhD research in the department of Inorganic Chemistry I at Ruhr-University Bochum, as a stipend holder from Graduate School of Solvation Science, GSS, RESOLV. She has had research stays in various scientific institutions in Spain, Italy and France including her GSS internship in Spain, and has attended several conferences.

A theoretical study to unveil the working cycle of an elusive enzyme causing tissue diseases

Living far from my family makes me look forward to every meeting with them. And here I am, just arrived at the airport, everyone is looking at me, smiling and asking lots of questions, including a dreading one: “Ok, tell us what your work is about?” For me, as a theoretical chemist, this is a mission impossible! Should I bore them with equations and certain words, such as quantum mechanics, level of theory, potential energy surface? It’s hard to be general while speaking about such a specific topic, but I shall give it a try.

In one of my PhD projects I investigate the working cycle of an enzyme called MMP-2 (Matrix Metalloproteinase type 2), finding out the important role of an acidic residue of the enzyme and of the surrounding water.

MMP-2 is located in tissues of animals and humans. It regulates the proper protein composition of the extracellular matrix by cutting collagens (structural proteins of the tissues). At certain conditions MMP-2 may get too active doing its job, it will cut gelatin too fast and too intensely, causing inflammation processes, tumors, metastasis and similar illnesses.

A long-range aim is to find a way to control the activity of MMP-2, for example by designing a molecule (a drug), that would block the active site of the enzyme and stop the excessive degrading of gelatin. But before doing so we need to know in detail how the enzyme works: where the active site of the enzyme is and what rearrangements occur during the chemical reaction. Unfortunately, the experimental techniques cannot give exhaustive information on all the chemical steps, this is where theoretical chemistry comes into play.

The theoretical models we construct are based on experimental data, but we must always keep in mind the approximations we make and the limitations of the theory we use. Nevertheless, our models let us see atoms in molecules, atom movements during chemical reactions, and we can also estimate energy penalties for chemical processes.

Enzymes are big molecules, therefore they are treated by a special “divide and conquer” computational approach, called QM/MM (quantum mechanics/molecular mechanics). Our MMP-2 model system was divided into two parts: a small part, where a chemical reaction takes place, was treated by accurate but computationally expensive (quantum mechanics) methods; the rest (the environment) was treated by fast “balls on springs” approximation, called molecular mechanics. By using this trick we managed to perform accurate calculations on big biomolecules in a reasonable computing time.

The following video shows the four main steps of a chemical reaction in MMP-2: 1. a water molecule attacks the substrate (ES → TS1 → I1)1, 2. O-H group rotates (I1 → TS2 → I2), 3. a proton is transferred from an oxygen atom to nitrogen (I2 → TS3 → I3), 4. a bond between carbon and nitrogen breaks (I3 → TS4→ I4). We see that the acidic residue (which is a glutamic acid) plays a crucial role in the chemical reaction and that water molecules act as a reagent. By not letting water into the active site or by changing a substrate in a way that at least one step of a chemical reaction cannot proceed we can stop MMP-2 from working.

I have also modelled a product release step and found out that it may very likely be a rate limiting step of the whole process. In a similar fashion, I’ve studied a mutant of MMP-2 as well.

At the end I’d like to say that a valuable scientific discovery can be made only with the combination of theory, experiment and something as simple as a groundbreaking idea.


1 The abbreviations stand for ES: enzyme substrate complex, TS: transition state and I: intermediate.

Link to Max-Planck-Institut für Kohlenforschung

About the Author

Tatiana Vasilevskaya was born in Minsk, USSR. She obtained her Diploma in Chemistry at Lomonosov Moscow State University. Currently she works on her PhD thesis at MPI für Kohlenforschung at Mülheim an der Ruhr in the group of Prof. Walter Thiel.

Your odds of getting a job at Bayer HealthCare in Wuppertal

Bayer HealthCare Wuppertal

Excursion team to Bayer HealthCare Wuppertal

On the 20th of April 2016 RESOLV organized a captivating excursion to Bayer HealthCare in Wuppertal. It was a great opportunity for us PhD students to get insider information about the many career possibilities and research areas in Bayer.

The trip began from Bochum with a bus transfer to the Bayer HealthCare (BHC) research center in Wuppertal, where Mr. Larsen Schnadhorst from the Communication department and Ms. Angelika Behling from the Human Resources welcomed us. Ms. Behling introduced Bayer to us: About 2,600 employees work in the Wuppertal site and half of them are employed in research; the site covers an area of 18 hectars and its focus revolves around the topics cardiology and oncology.

Behling also told us about the philosophy of Bayer and briefed us about how to apply for and what to expect from Bayer. Here came some interesting information for a PhD student! For example she told us about PhD-workshops organized in cooperation with Germany and USA: To take part in these workshops you have to fill an application on their web-page – If you get accepted, Bayer will cover the costs. There are also special graduate programs including international trainee Programs for chemists, engineers or computational scientists. Getting a Post-Doc position is almost a bet, but in case of acceptance you would get a three-year contract with a follow-up contract being likely. Concerning direct job applications, two routes can be taken: 1) It is possible to start as a head of laboratory in R&D with one or two technicians. 2) You can start a career in a manager-position, rotating between different places every few years. Jobs like patent attorney or business consultor are also possible alternatives.

After this presentation the lab-station visits began. At the ophthalmology laboratory we were shown the structure of a human eye and what kind of things could happen with your eyes – e.g. the retina – when getting older. We could see damaged eye cells of rats under a microscope and how rats with induced eye diseases are examined in order to develop drugs that could possibly help humans in a later stage.

At the medicinal chemistry department we saw how drugs are synthesized and investigated. It was at the newly found catalysis department that we discover how professionals can also come across with some technical problems sometimes leading to high amounts of expenses or even the abortion of the project. However, given a second chance in many cases the problem is solved.

At the cardiology department we got to know about the manufacturing of drugs against thrombosis or hypertension. Researchers use mice or rats to test the effects of the drugs and we were shown how they conduct animal experiments and what equipment they use. From explanatory videos we could see how thrombosis can be induced mechanically in living but anesthetized mice and how special drugs can prevent it.

After our six hour excursion we were tired but happy that we got so much first-hand information about a pharmaceutical company. Now it was time to get back to the Ruhr-University Bochum.


About the Author

yesimmuratYesim Murat, born 1987 in Schwäbisch Gmünd, has studied Chemistry at the Karlsruhe Institute of Technology and obtained her diploma in 2012. Since 2013, she works as a PhD student in the field of Synthesis and Characterization of Ceria-Zirconia Catalysts for the liquid-phase Dimethyl Carbonate Synthesis at the Fraunhofer Institute UMSICHT in Oberhausen (Germany) in the Catalytic Processes group of Dr. Stefan Kaluza. Prof. Dr. Martin Muhler is supervising the thesis on behalf of the Department of Technical Chemistry at the Ruhr University of Bochum.

 

Traditional RESOLV ECR Football Tournament 2015

The tradition continues. As part of the annual Early Career Researcher Summer Party of the Cluster of Excellence RESOLV, the ECR Football Tournament (NC-Fußballturnier) took place on 16 September 2015 at the football field behind the GB Building.

The Players Greeting Each Other

The Players Greeting Each Other

All groups within the Department of Chemistry and Biochemistry were invited to participate. The participants of this year were “Photonics” from the work group of Physical Chemistry II, Physical Chemistry I, “Elanos” from Analytical Chemistry, “Schlenkchester United” from Inorganic Chemistry and “AK Huber” from Organic Chemistry I. Since there were only five teams, every team had chance to play against each other simultaneously on two different courts. After this exciting period from 10:00 am to 2:30 pm, the teams of the final match were decided.

After a break, the final game started and everybody hold their breath: The winner team was “Photonics” again, for the fifth time since 2011, so they get five stars now.

The Winner Team "Photonics"

The Winner Team “Photonics”

The winners of the previous years were “Real Chlorid” in 2005 and 2006, “Verwaltung” in 2008, “Reaktor 04”, “O Zeh Zwo” in 2009 and “Reaktor 04” again in 2010.

Barbeque After the Tournament

Barbeque After the Tournament

Drinks and BBQ were not also forgotten after the tournament. Even though there was a little drizzle, it was a thrilling and joyous tournament.  The eyes are now on the next year’s tournament.


The more detailed information about the event can be found in the poster below:

ECR-Football_Poster

From the Perspective of a New iMOS Student

When I thought about doing a Master’s degree, the image in my mind was to follow my dreams. I always had the ambition to learn more in detail about the physical world around me. It was the world of atoms and molecules which was quickening my pulse and whispering me: “Apply for a Master’s program on molecular simulations and spectroscopy”. That’s how I found out about the iMOS program. Then started the journey of applications.

The application to the iMOS program is very easy. One of the things that you may like is that in Germany, most of the universities do not require an English language test such as IELTS or TOEFL if your language of study was English in your Bachelor’s degree. The rest of the documents are mostly to be sure that you are applying for the program that you really want to study. You can find the whole set of required documents from the iMOS web page.

Now, I want to talk about my visa application process, because it can be very daunting for the applicants from non-EU countries. I am from Turkey and this was the first time for me to go abroad. So the whole process was very unfamiliar to me. There is a list of required documents which you can check from the embassy’s website for a national visa for educational purposes. For me the most time consuming part of the story was to get the proof of my financial resources. There are a number of ways to do it. You can present a scholarship award notification which makes everything easier. You can also get a guarantee, if someone with permanent residence in Germany is willing to take responsibility. This guarantee, called “Verpflichtungserklärung” in German, can be get by your guarantor. If you can get hold of one of these this would be a good option.

Another option is to open a blocked account which is what I used for my visa application. You need to make a security payment with an amount of one year of living expenses. This was a minimum of € 8,040 during my application for visa. But there is also € 50 fee billed for the registration of blocking account, so you need to transfer at least € 8,090 to the account. The procedure is different for each bank. In my case, I opened the account from Deutsche Bank. For the case of Deutsche Bank, you need to sign the application form in the presence of an embassy official. For this approval I got an appointment online and went to the embassy with my passport and admission letter. This approval cost €20. Afterwards, I posted the application form to the Hamburg branch of Deutsche Bank together with my admission letter from the university and a copy of my passport with express post. Unfortunately, it took more than a month for the post to reach because Deutsche Post was on a strike. In the following week I got an e-mail regarding the opening of my bank account. Then I delivered the required amount via a SWIFT.This also takes a few days. After the money transferred, I got a second e-mail proving the blocked amount.

And voilà! This is the document that you need to print out and give to the embassy for your visa application. If you survived until now nothing can stop you. In my case it took even longer than getting my visa. Including the time I spent to get the required documents, in total it took around two months to get the visa. So I recommend you to do everything as early as possible so that you can cheerfully buy the cheapest ticket without carrying the worry of not getting the visa until then.

The first place I came to was not Bochum. I went to Munich to visit a friend from university. Meanwhile I had the chance to have a smooth adaptation period to the German culture. It might sound funny but the first moment I saw a squirrel was very fascinating for me. It was the first time in my life that I was seeing a living squirrel. But it is a usual thing in here. Because in Germany they have a lot of oak trees. Oak tree is called “Eiche” in German, and a squirrel is called “Eichhörnchen”. I think, it is also a cuddly word to pronounce.

View from the top of Hoher Fricken facing Kloster Ettal

While in Munich I also went hiking in the Alps. We climbed the Hoher Fricken, a mountain in the Bavarian Prealps. There was a little fog in the morning but it faded and a sunny day encouraged us. We came across with a lot of nature lovers during our walk. There was even a woman who was hiking with her dog. I strongly recommend you to see the Alpine region. If you go to Munich, also keep in mind that on Sundays the entry fee to most of the museums is only € 1. During my time in Munich I also had chance to listen some seminars in the Max Planck Institute of Biochemistry in Martinsried. The Max Planck Society is one the biggest societies in Germany in research. As a person interested in natural sciences, life sciences, social sciences, and/or the humanities you will be fascinated with this society and they are everywhere in Germany!

The orientation week was to start at the third week of October. Therefore, I bought my ticket to Bochum for the beginning of October so that I had enough time to settle. The cost of a room is generally € 260 per month. My room was without furniture but I found almost everything for free. If you are also considering renting a flat without furniture, it is not that hard to find cheap or free furniture, though it will take some time and effort. I enrolled to the university and applied for the residence permit in the first week of October. However, you can also do these in the orientation week, because there are volunteers helping you. But if you want to extent your residence permit yourself, I can explain briefly. You should first register at the city with your contract for your flat. Now with your approved address, you can apply for the activation of your Deutsche Bank account and discharge required amount for the visa extension fee, if you don’t have it in cash already. For the visa extension you need to get an appointment from the Foreign Citizens’ Office and go there with the required documents. When I was finished with those I was very eager to start the lectures.

19th of October, I met with the other iMOS students. It was Lisa who suggested this small meeting just before we were going to our first lecture. Now I am in my third week and it is fascinating to get more into spectroscopic techniques and molecular interactions. As a part of Dynamics and Simulation course we also make simulations using GROMACS package. For example, this week we calculated diffusivity of Argon in Argon for solid, liquid and gas phases looking at the change of mean squared displacement within time. Maybe it does not sound very fancy but when you know the basics, you can put on it! We also have courses on quantum mechanics, thermodynamics and statistical mechanics which are very supportive to understand the other courses in depth.

Now after my first month in Bochum, I can say that there is a lot to live here. I already feel like at home. Here the nature touches your soul. I regularly join the running group of the “Hochschulsport” of the Ruhr-Universität Bochum and enjoy the beauty of Kemnader Lake and the forest. If you are interested there is also a Music and Arts Center in the university. Here, I am practicing piano. To take a little break I sometimes go the studios and work there with wood, paints, etching in brief almost anything you would like work with. You can work on your own or you can take courses. To be allowed to use these studios, you need to pay € 35 per semester but it includes the materials as well.

I am wondering what the future will bring, but now I feel like I am following my dreams.


About the Author

oezlem-yoenderÖzlem Yönder was born 1991 in Ankara and holds a BSc in Chemical Engineering from Middle East Technical University, Ankara. After her degree, she started a Master’s program there; however, after deciding she wants to learn in depth molecular simulation and characterization techniques she didn’t complete her MSc degree in engineering. Instead, she currently studies in Molecular Sciences with a Focus on Spectroscopy and Simulation (iMOS) program at Ruhr-Universität Bochum.