David van der Spoel

On the hunt for new models

David van der Spoel never planned to get involved with biology or computers, but now he does both. A lot of it is down to chance, he says, explaining that after initially studying physics he is now engaged in computational chemistry- and biology research. His main objective is to develop software and physical models to simulate chemical and biological systems such as proteins, lipids and nucleic acids. The GROMACS software that he develops is used by thousands of scientists all over the world.

He has recently become interested in how environmental toxins affect living organisms. This new research work started just over three years ago, when he read in the press about the sudden deaths of some ten moose in Blekinge and southern Sweden.

“It had been suggested that the moose died of vitamin B1 deficiency, and a potential cause was that their vitamin B1 absorption had been blocked by environmental toxins. My interest was raised, and we looked for potential interactions between vitamin binding molecules and common pollutants. We recently published a study highlighting some candidates that might block vitamin B1 absorption in the body,” explains David van der Spoel, "but further evaluations are needed"..

He thinks it strange in itself that herbivores such as moose should suffer vitamin deficiencies. All plants produce vitamin B1, after all. If non-natural chemicals such as PCBs, dioxins or substances used in agriculture block the vitamin absorption system, it might indirectly affect the entire ecosystem. 

“Some environmental toxins have molecular structures that resemble vitamins. We can use simulations to see how molecules interact with each other and this helps us to better understand the underlying mechanisms. Not many teams are studying environmental toxins in the way we are,” says David van der Spoel.

Simulation models are useful in many contexts, like for studying how proteins fold into their characteristic 3-dimensional structures. The research team was able first of all to reproduce a protein structure entirely on the basis of a simulation model.

Some years ago, the research team used a simulation study to describe what happens when a virus particle opens up and how water can penetrate where calcium ions usually keep the viral envelope intact. The ions probably come free during an infection, allowing small pores to form in the capsid. These then admit water, and the virus swells. Such viral infections are of great interest. The research team is also studying the virus that causes dengue fever. Here too, they are looking at virus infection into the cell through the cell membrane. The research is being carried out in collaboration with a Brazilian research team.

Simulation is a very useful tool for studying liquids and simple solutions as well, when using sufficiently accurate physical models:

“Although water and e.g. NaCl are relatively simple molecules, there is still a lot about them that is difficult to model, such as crystal formation. It is essential to get these fundamentals right in our models before we tackle more complicated problems,” says David van der Spoel.

They final goal is to be able to ‘see’ the chemical and biological processes in atomic detail. It is very challenging to get one model that describes everything, partly because there are just so many organic compounds including macromolecules like DNA, RNA, protein, etc., says David van der Spoel, but we are working on it.