The chemist with a handle on the state of molecules

4 december 2018

Erik Marklund is a researcher in Biochemistry at the Department of Chemistry - BMC: “There is a great deal of information available when one knows where all of the atoms are over time”.

How can proteins be influenced so that they point in a single direction? And what role do proteins’ interactions play in biology? The biochemist Erik Marklund uses computer calculations to reveal the dynamics between vital molecules.

Despite all of the knowledge about the important work that proteins do in living organisms, there is still a lack of deeper knowledge about how different protein components interact. In his research, Erik Marklund uses computer simulations to understand how the interactions in a cell or organism affect one another.

“It’s a lot about letting the computer simulate the laws of physics so that the atoms affect each other with different forces. This way, we can get the atoms to move and interact as we believe they do in a test tube or a cell, for example,” says Erik Marklund at the Department of Chemistry at the Biomedical Centre, BMC.

Erik Marklund uses the computer cluster
in BMC’s basement in preparation of
larger calculations: "What would take years
to do on an individual computer can be 
calculated many times faster down here”. 
Photo: Mats Kamsten

His research team is investigating biological systems that are often involved in the progression of a disease. Even if focus is on concrete applications, the team’s computer calculations are very useful in experiments in, for example, the molecular life sciences.

“Based on my calculations and the given conditions, I can make a prediction of what readings our partners would get in an experiment. It’s a kind of hypothesis testing,” says Erik Marklund.

“There is a great deal of information available when one knows where all of the atoms are over time – it’s almost too much. One really has to be selective.”

Right now, he and Carl Caleman at the Department of Physics and Astronomy are working on an idea they developed to manipulate proteins in a gas phase. This is what the state is called when proteins are moved from a kind of water solution to a vacuum environment where they can fly freely. Using strong electric fields, the researchers try to orient the proteins to point in the same direction to facilitate attempts to determine their structure. Making calculations on intact proteins in a vacuum is an area in which Erik Marklund has distinguished himself at an international level.

 “We are now continuing with theoretical calculations of how we can orient proteins without destroying them. This is what is unique and nobody has done this before.” 

The experimentalists use mass spectrometers to select specific proteins from a sample. Then, the proteins are oriented with electric fields and subjected to high intensity X-ray pulses. This also opens opportunities for cooperation with business and industry. Erik Marklund’s research team recently secured extensive financing in a consortium where an instrument manufacturer is currently developing a prototype for protein orientation.

He also hopes for a new collaboration with a company in the U.S. that makes its own mass spectrometry instruments. New types of analysis tools for biological pharmaceuticals are needed to more quickly be able to determine if the end product fits the bill. Another dilemma with biotechnology products is that they fall apart over time.

“You cannot have them on a pharmacy shelf as long as traditional medicine, for example, because these protein-based medications have somewhat short expiration dates. Consequently, there is a somewhat large financial value in extending their lifetime and making them more stable so that they don’t spontaneously become inactive. This is where we believe we can optimise the stability, among other things with the help of the manipulations we do with electric fields.”

His interest in the area was incited when he was attending the engineering programme in molecular biotechnology in Uppsala and saw simulations of how the atoms in a protein moved. Another eye opener was the course in X-ray crystallography about proteins’ structure and shape.

“A third important thing was probably when I did a degree project working under Janos Hajdu and David van der Spoel at the Department of Cell and Molecular Biology. One day I was sitting in the lunch room with the others in the doctoral programme, Professor Hajdu showed up and said ‘we have these collaborators who have the purest diamonds in the world and we would like to go to California and shoot X-rays at them and measure them in various ways. Do we have any volunteers?’ Of course, I didn’t think this was directed at me as an degree project student because there were a bunch of doctoral students and post-docs there. But nobody reacted so I raised my hand and he immediately said ‘you, come to my office!’ And so the professor sent me off to California where I got to conduct experiments at Stanford University for a month. It was a good introduction to research at a very high level!”

He began his doctoral studies in 2006 and already then conducted molecular dynamic simulations of proteins in a gas phase. After earning his PhD in 2011, he did his post-doctoral fellowship with Johan Elf at ICM with further focus on interactions between proteins and DNA, as well as analyses of microscope images. A number of discussions with two research teams in Oxford piqued his curiosity, and he succeeded in getting grants to conduct research at the university’s chemistry department. His family joined him, his girlfriend a political scientist who had just gotten her own post-doc financing and their twin five-year-old boys.

“Something I learned at Oxford, besides the purely scientific, was what successful leadership looks like and how a research team can be both productive and pleasant to work in. It was a valuable experience because I’ve also seen several examples of teams around the world that practically crush their doctoral students or in any case risk doing so.”

After three years, the family returned to Sweden in 2016. Erik Marklund had then gotten a good offer from the Biomedical Centre together with a Marie Curie grant from the EU and the Swedish Research Council.

Do you have any advice for students who are interested in your field?

“Get in touch! I’m happy to welcome degree project students who want to try working in my domains. You should remember that you don’t have to be a full-fledged computational chemist to be able to do a meaningful degree project. We’re all beginners at some stage.”


Anneli Björkman



Age: 38

Title: Researcher in Biochemistry at the Department of Chemistry - BMC

Greatest research success: Software I wrote at Oxford – IMPACT. It has been of use for many people and taught us a lot about protein structures. The Science project earlier this year also comes to mind, where we succeeded in explaining how two kinds of shock proteins with common origins successfully avoid forming complexes with each other. This is even though they practically have identical contact surfaces and have no problem forming complexes with other proteins in their own classes. This began more than 400 million years ago when a gene was duplicated and gave rise to the two protein classes, which since then occur in all land-based plants. With our results, we were able to find certain principles that seem to apply to protein complexes more generally.

Leisure activities: As much Brazilian jiu jitsu as I have time for. I spend a lot of time with my family so it helps that they also whole heartedly pursue the same noble sport. I draw and play a little music too, but unfortunately there are only 24 hours in a day and you have to sleep sometimes.

Reading: Preferably Sara Lidman. Right now, a biography about Dorothy Crowfoot Hodgkin

Listens to: Quite a bit nowadays, but folk music, punk and black metal deserve extra mention in this context. I have played music since I was quite young, but only on an amateur level. Especially in England, I played quite a lot of Swedish folk music. My partner plays the hurdy gurdy and I picked up the accordion a few years ago. In England, we met some folk musicians who taught us British pieces and we taught them Swedish-Finnish folk music.

Wanted to be when I was little: A scientist actually. Although I never even thought it was theoretically possible. There were some educated people and intellectuals in my surroundings during my childhood in Piteå, but nobody who worked with pure science.

About Uppsala: A beautiful and inspiring city. But I seem to still be a Piteå native, heart and soul.


Read more:

New knowledge about membrane protein - important for the cancer medicines of the future

Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions

More about the research in biochemistry at Uppsala University and Marklund’s research team

Contact information Erik Marklund