Frame by Frame, Supercomputing Reveals the Forms of the Coronavirus – HPCwire

From the start of the pandemic, supercomputing research has been targeting one particular protein of the coronavirus: the notorious S or spike protein, which allows the virus to pry its way into human cells and thus enables its infection of the human body. As a result, finding ways to attack or neutralize the spike protein is the cornerstone of much of the research on COVID-19 vaccines and therapeutics but that research is complicated by the extraordinarily computationally intensive tasks of simulating the spike proteins various forms and binding vast numbers of molecules to those forms. Now, a duo of researchers from the University of California, Berkeley, and Istanbul Technical University are using supercomputing at the Texas Advanced Computing Center (TACC) to elucidate the most minute movements of the spike protein.

Spike protein-adjacent simulations have been near-ubiquitous in supercomputer-powered coronavirus research and the researchers know where they fit into that crowded landscape. Many groups are attacking different stages of this process, said Mert Gur, vice dean of the mechanical engineering department at Istanbul Technical University, in an interview with TACCs Aaron Dubrow. Our initial goal is to use molecular dynamics simulations to identify the processes that happen when the virus binds to the host cell.

Essentially, this involves four steps: first, the spike protein opens; second, it binds to the ACE2 receptor on a human cell; and third, that binding transforms the spike protein, which is split in two; and finally, the split spike protein forces the host cell to admit viral RNA. While the broad strokes of this process have been known since early in the year, the finer details of the movements of the spike protein between its fixed states have remained shrouded in relative mystery.

Gur and his colleague Ahment Yildiz, an associate professor of physics and molecular cell biology at UC Berkeley used an allocation on TACCs Stampede2 supercomputer (obtained through the COVID-19 HPC Consortium) to study these intermediary forms. A Dell EMC system, Stampede2 is equipped with Intel Xeon Phi CPUs and rates at 10.7 Linpack petaflops, placing it 21st on the most recent Top500 list of the worlds most powerful supercomputers. Yildiz and Gur performed all-atom simulations of the spike protein on Stampede2 and the results were illuminating.

We showed that the S protein visits an intermediate state before it can dock to the receptor protein on the host cell membrane Gur said. This intermediate state can be useful for drug targeting to prevent the S protein to initiate viral infection.

But the research went beyond just finding these intermediary states. The researchers worked to identify the individual amino acids that stabilize each state, aiming to find a way to introduce roadblocks in the physical changes of the spike protein.

If we can determine the important linkages at the single amino acid level which interactions stabilize and are critical for these confirmations it may be possible to target those states with small molecules, Yildiz said. Its a computationally demanding process, but the predictive power of this approach is very powerful.

The initial findings of this research, which have already been published in the Journal of Chemical Physics, were validated using lab experiments.

To read the reporting by TACCs Aaron Dubrow, click here.

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Frame by Frame, Supercomputing Reveals the Forms of the Coronavirus - HPCwire