APEIRON’s „Three questions to“

Prof. Chris Oostenbrink

1. How can computational techniques allow to study the effects of mutations of SARS-CoV-2 ?
Computational methods allow us to describe molecular interactions at a space and time resolution that is often unattainable experimentally. This means that we can zoom in at an atomic level to understand visualize, rationalize, and predict what the effect of mutations of SARS-CoV-2 may be. Using statistical mechanical methods, we can, for instance, quantify the relative binding affinity of a mutated Spike protein against the ACE2 receptor. This will give insight into the mechanisms by which mutations change the behavior of SARS-CoV-2.

2. What is so special about the coronavirus ?
For us, as computational chemists, it is amazing how quickly there were high-quality structures available. We were able to complement these with the appropriate glycosylation and then to use them in molecular simulations.

3. How can the interaction between SARS-CoV-2 and its cellular receptor ACE2 be described ?
This is a highly complex interaction. First, it seems that glycosylation on both the viral Spike protein and on ACE2 affect the interactions. Some glycans directly strengthen the interactions, while some glycans on ACE2 rather seem to hamper an even more efficient binding. By using molecular simulations, the structure and the dynamics of the interactions can be described at an atomic resolution.

Reference:
artistic picture of a 3D-printed model of the SARS-CoV-2 Spike-ACE2 receptor interaction made by Dr. Oostenbrink and colleagues (courtesy of Chris Oostenbrink and cloningcompany.at)

Movie:
SARS-CoV-2 Spike / ACE2 interaction (courtesy Chris Oostenbrink)

About CHRIS OOSTENBRINK:

Prof. Chris Oostenbrink studied both theoretical chemistry and pharmaceutical sciences at VU University in Amsterdam and graduated in both curricula in 2000. He continued with a PhD project in physical chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich, then he returned to Amsterdam as an assistant professor at VU University in Amsterdam, leading a group for computational medicinal chemistry and toxicology. In 2009, he was awarded a Vienna Science Chair of the Vienna Science and Technology Fund (WWTF), allowing him to start a group for biomolecular modeling and simulation at the University of Natural Resources and Life Sciences (BOKU) in Vienna. He was awarded an ERC starting grant in 2010 and was promoted to full professor at BOKU in 2015. Chris’ research focuses on the development and application of methods in molecular dynamics simulations, with a special focus on the calculation of free energies.