How Is Folding@home Helping Coronavirus Research?

Bowman’s group was already focused on other infectious diseases when a member of his team began simulating one of COVID-19’s proteins. Quickly it dawned on them that they should be exploring all of the disease’s proteins to try to understand where potential remedies could be most effective. Bowman explains that one part of the process is simulating how certain chemical compounds bind most strongly to proteins in particular sites, helping their partners narrow down the options while developing remedies.

“This is really valuable because our experimental collaborators — they can do a lot, but they only have finite resources, so they can’t buy every possible chemical that you could potentially make and synthesize those and do the experiments,” says Bowman. “What we’re able to do is help them prioritize compounds that are more likely to work than others.”

Folding@home began in late 2000 and has continued on over the years, just moving under Bowman’s direction in 2019. He says that the original idea for the project was to figure out how the process of protein folding leads to the various maladies they were investigating.

“It’s as if you took all the components of your car and laid them out in a line on the street, and they spontaneously on their own, without anyone assembling them, sprung into place and formed a functioning car,” he explains. “It’s like: wow, how does that happen? And so the idea was that if we could solve problems like that, then we’d be in a position to tackle all kinds of other more immediate, biomedically relevant problems.”

Trying to find out where drugs could potentially bind to a protein in a disease is something that Bowman’s group was heavily focused on with Ebola, before pausing due to coronavirus. Now it’s something they’d like to apply to the current pandemic.

“Often, proteins don’t have any attractive sites for a drug to bind tightly. But when we go in with our simulations and look at what the proteins do, besides the most usual structure that you can see experimentally, we often see the spontaneous formation of appealing-looking sites for drugs to bind that we call cryptic pockets,” says Bowman. “We’re set up then to experiment with tests to see if these pockets are real, and test whether targeting them has the desired functional impact on the proteins-and then to start designing drugs to bind with them.”