Researcher Profile: “The idea is to derive new generic molecular models”

10 oktober 2019

David van der Spoel is Professor in Biology, specialising in Molecular Computational Biophysics, and Head of the Department of Cell and Molecular Biology.

With the aid of computer simulation models, David van der Spoel isolates the mechanisms behind molecular interactions. These models can predict the properties of a drug, or an environmental toxin’s ability to penetrate the cell membrane. “There is a lot of research being done on drugs to make us better when we get sick. But it’s just as useful to research substances that make us sick in the first place.”

Interdisciplinary research is an appropriate description for the activities in David van der Spoel’s lab at the Biomedical Centre. Even though it is not a lab in the literal sense of the word. Because – computer scientist that he is – David works in a normal office room, surrounded by computers and screens. There he develops and improves data models that can be used to mimic the dynamics between molecules in liquids and virus particles, for example. Simulating such complex chemical and biological systems requires knowledge in chemistry and biology as well as in physics and computer science. All fields that he himself has substantial experience in.

“The first time I studied physics at university was at home in Groningen. But then my interest in chemistry and biology took over and after that, computer science. So it has been quite a windy road to where I am now within the Computational Biology and Bioinformatics programme.

David van der Spoel began building a simulation program while still living in the Netherlands. It is called GROMACS, and is now used by thousands of research teams around the world. The program makes it possible to analyse liquids, lipids, proteins and nucleic acids, and took him many decades to design and refine, as part of an international network. And there is still room for improvement of the program.  He sees algorithm development and machine learning as important pieces in the puzzle for designing better models and being able to apply them.

“Different chemical substances have different kinds of molecules and the complexity is enormous. Even though we can buy or create molecules, the design variants you can imagine are infinite,” says David van der Spoel.

One example is drugs. It’s important to be able to predict their properties before ordering the molecules, since producing them can otherwise get very expensive, he explains. It is also a reason why many medical students and drug developers are using GROMACS today.

“The idea is to develop a model that you can use with all the different types of molecules: proteins, DNA, RNA, and so on. One of my doctoral students has made some progress in building and testing this kind of software, and some research colleagues have developed other parts of the model. It’s going slowly, but surely.”

Another goal of the program is to assure the reliability of the data entered in the simulation models. In parallel with GROMACS, David van der Spoel and his research team are developing a model called Alexandria. It gets its name from the Egyptian city with its once legendary library. In ancient times, visitors were forced to leave all the books and scrolls they had brought with them for copying and archiving in the library, which meant that everything that had ever been written down would be saved for posterity.

How much material was saved when the library in Alexandria was destroyed is unclear. But the digitisation of research results in our time has opened up new opportunities for collecting, storing and questioning data.

“Many data points were discovered long ago by researchers who are now dead and their publications are difficult to access. But many of these are in databases, collected by people in the 1970s and some were copied in the 1980s. However, there is a risk that the original data will disappear or at least become difficult to access. In the Alexandria project, I have tried to collect and review this kind of data on the characteristics of molecules,” says David van der Spoel. He adds:

“Of course I have found some errors too. But if you send an email to the researcher, the response you get is sometimes ‘Oh, I haven’t looked at that data for twenty years, but great, I will correct it’… That’s why the project is called Alexandria, because we are trying to achieve as comprehensive a collection as possible and also to correct errors in it so that the data can be used.”

His original interests in biology and the environment have also found their way into his research. Among other things, he has used his simulation models to investigate environmental toxins and their potential impacts on biological systems. A recent article from his research team explores whether environmental toxins can penetrate the cell membrane. The researchers’ hypothesis is linked to reports of emissions of perfluoroalkyl substances (PFAS) at the old airport in Ärna outside Uppsala. The Defence Force’s fire-fighting exercises ended up leading to pollution of drinking water in the area.

“Because these substances are fairly new, there is very little data about them,” says David van der Spoel. “With our simulations, we have tried to add to the data, so there is now new information about how easily these substances can penetrate a cell membrane.”

The researchers have chosen 130 substances in two or three categories of environmental toxins, including these fluorinated substances, and calculated how much energy it costs them to penetrate a cell wall. David van der Spoel shows a film that illustrates how difficult it is for a toxin molecule to penetrate a membrane.

“What we can see is that the energy barriers that arise are different for different molecules. Some get in through the membrane, but the question is, what happens next? There is so much that we don’t know.”

Another thing that the research group also needs to explore is the combined effect of several different toxins, including endocrine disrupting parabens that bind to oestrogen receptors.

“However, these kinds of substances are at least found in nature, where some break down and others do not. For these, we will continue to run calculations on how easily they can get into cells.”

In addition to research, David van der Spoel is also engaged in environmental issues related to sustainable forestry. As a teenager, he was a member of the equivalent of Nature and Youth Sweden (Fältbiologerna) in his home town of Groningen. But studies and work got in the way and his engagement with these issues fell by the wayside.

“But about ten years ago I thought that I have to do something more, I cannot just leave it all to the next generation so I decided to become more active.”

He found a group on Facebook, Protect the Forest, where he began to contribute posts. Very soon he was asked to join the board, and he also became the spokesperson for the group for several years. During that time, he wrote 50 or more op-eds and letters, which he continues to do even now to a lesser extent. In these op-eds, he stressed the importance of conserving natural forest and safeguarding biodiversity among other things.

As a researcher, what are the problems you see in taking on these issues?

“You see, I think that researchers should be listening to research from other disciplines then their own. Ignoring the recommendations is a dangerous path ultimately of course, and we know now for example that it is not healthy to smoke, it’s something that research has concluded. Then society takes action, step-by-step. But in terms of the environment and the climate, not enough has happened. Even though we know how things stand.”

David would really like to combine his engagement in environmental issues with research to a greater degree. But getting funding for research in a new field is tough.

“Of course it would be fun to do something with all the knowledge I’ve accumulated. But at the moment, my focus is on making the Alexandria model usable.”


Anneli Björkman



Age: 56

Title: Professor in Biology specialising in Molecular Computational Biophysics and Head of the Department of Cell and Molecular Biology.

Family: Wife and three children who are 23, 26 and 28 years old. My oldest daughter studied biology at Uppsala and is now a consultant in ecotoxicology. Another of my daughters has taken after my wife and is a nurse, while our youngest daughter has started studying environmental science at the Swedish University of Agricultural Sciences. Even though I haven’t pushed them, our children have followed in our footsteps to some extent.    

In my spare time: I like to take photographs, especially of birds and insects, and go on hikes in the Swedish mountains with the family. Our youngest daughter was studying in Scotland for some time, and we travelled there a few times. But for environmental reasons, I don’t fly, so we went by train. It took two days of course, but that gave us the opportunity for a stopover with relatives in the Netherlands. 

Reading: I recently read the book A Sting in the Tale by British professor in biology Dave Goulson, which was an eye opener in many ways.

Strength: I am quite open to new findings on the research front. A while ago I received an email from a person who disputed one of my conclusions in a scholarly article. After having read his comments, I concluded that he was right. He was very taken aback when I conceded this. Apparently he had had bad experiences on that front. That’s another reason why I get into debates with people who talk about things in simplistic terms and don’t take the trouble to dig into the details about the impact of environmental toxins on biodiversity for example.

Weakness: I haven’t been as focused as you are supposed to be as a researcher – I’ve found it a bit too easy to get distracted. This has probably meant that I have lost time and also competitive advantage.

About travelling to conferences: I’m going to a conference in Lausanne soon, and that will mean taking the overnight train from Hamburg to Switzerland. I probably do two or three trips each year, but only within Europe. I don’t make a big deal out of my decision not to fly. The University ought to be questioning the necessity of all flights, but we are not there yet.

When I was young I wanted to be: A musician.


Read more:

Publications by David van der Spoel et al:

Prediction of Partition Coefficients of Environmental Toxins Using Computational Chemistry Methods

Systematically improved melting point prediction: a detailed physical simulation model is required

More about David van der Spoel and his research in the van der Spoel lab at Uppsala University