How virtual reality and high-performance scientific computing are helping scientists understand how COVID-19 behaves
On Thursday February 20th, Dr Michael Kuiper stepped into cryo-EM 2019-nCoV spike protein structure of COVID-19. The virus had infiltrated a protein within its host, utilising its uniquely virulent composition to take over the individual’s biological processes, transforming a once healthy cell into a mass of viral particles.
“See this? This model shows the same lysine and tyrosine residues as the SARS spike protein, but there are new amino acids and new hydrogen bond interactions, too,” explains Dr Kuiper. “The authors of the recent paper measured the strength of this interaction at 10 – to 20 – fold higher than SARS. They speculate that this is why it may be so virulent this time around.”
While you’ve likely realised Dr Kuiper wasn’t physically inside the structure of COVID-19, it’s the world he steps into while using virtual reality (VR), supercomputer generated simulations and Nanome, a collaborative software platform for molecular visualisation and design to understand the behaviour of the virus.
Dr Kuiper is the team leader of the Modelling and Simulations Team at CSIRO’s Data61, who specialise in computer simulations ranging from quantum mechanics simulations of small molecules, all the way to industrial scale machinery.
By using computer modelling, he’s able to generate an accurate replica of COVID-19 to identify the regions of its proteins that could be good targets for vaccines.
“When protein 3D structures are solved with X-ray crystallography or cryoEM, we need to visualise them to understand how they fit together and how they function,” explains Dr Kuiper.
“We go a step further and use these ‘static’ structures to make computer models where we can see how they move in solution. VR provides an intuitive 3D way to visualize the data, making it much easier to interpret than a regular 2D monitor. It can also do so in a collaborative setting, such that people from remote locations can work together.”
It’s these VR and simulation capabilities that have enable Dr Kuiper to understand vital intricacies of the virus, such as why the interaction between the invading and host protein is so strong.
“(After stepping into the structure, I can see that) there seems to be a number of new hydrogen bond interactions that were not present in SARS/ACE2: Y498Q–K493Q–S501N, and a new salt bridge between D406E and V417K.”
Being able to explore the internal structure of a molecule is key not only to designing a successful drug, but also minimising the costly development process.
“As we can step into the active site of a molecule, we can modify a drug as it sits there to see how it might fit better, or design a whole new one from scratch,” says Dr Kuiper.
“The advantage of this is you can optimise the structure in real time to see how it fits, easily stepping back if you’ve made a mistake. This helps us decide what to make in real life to test in the lab, as that is the most expensive and time-consuming part. This greatly speeds up the drug development process.”
According to Dr Mark York, Group Leader of Biomedical Synthetic Chemistry at CSIRO Manufacturing, this methodology has the potential to drastically reduce the experimentation process.
“Modulating this interaction could provide a pathway to developing drugs to treat COVID-19 and other related members of the coronavirus family,” explains Dr York.
“With access to the model, potential drug candidates can be visualised to predict how they might effect binding and this can assist with prioritising which compounds to make in the lab from the huge number of possibilities. This has the potential to drastically reduce the time this process would take.”
While Nanome provides a platform to see the data up close and collaborate with experts across the world, CSIRO’s high-performing computer system Bracewell supplies the technological muscle needed to create the simulations.
Bracewell’s supercomputing abilities are enabling Dr Kuiper to achieve results significantly faster, with the device’s hundreds of central processing units (CPUs) processing the immense amount of data needed to scale simulations of COVID-19.
The remote visualisation nodes on CSIRO’s supercomputers also allow researchers to interact with 3D models in real–time, tuning simulation parameters at runtime as required, a useful requirement for a situation that is repeatedly progressing.
“In these unprecedented times, it has been amazing to see how quickly and freely scientific information has been generated on COVID-19,” says Dr Kuiper.
“Through Nanome and other collaborative online platforms and tools, we have connected with many scientists across the globe discussing various aspects of COVID structures and improving the models. “
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