By Daniel Dunaief

They know what happens. They’re just not sure how it happens.

Carlos Simmerling, Marsha Laufer Endowed Professor of Physical and Quantitative Biology and Professor of Chemistry at Stony Brook University, has spent over 22 years trying to answer the question of how processes at a molecular level occur.

Using chemistry, physics and computer programs he helped create, Simmerling determines the intermediate structural changes that occur with biomolecules such as nucleic acids and proteins, which would be extremely difficult to impossible to do at a bench or in a laboratory.

In March, as the United States was in the beginning of various school and office lockdowns in response to the spread of the pandemic, Simmerling endured the same discomfort and loss of control.

Researchers at Brookhaven National Laboratory, including Kerstin Kleese van Dam, Director of the Computational Science Initiative, reached out to Simmerling to see if his lab might use their experience and tools to understand the spike protein on the coronavirus that causes COVID-19.

Except for two people who were on the cusp of finishing their PhD’s, everyone else in the lab “shifted to work on this instead. We put everything else on hold and it’s been nonstop since March.”

Simmerling said he and his lab group decided at a special lab meeting on March 13th that it was important to contribute whatever they could to this unprecedented crisis.

Without the same kind of restrictions or limitations that lab groups that depend on working at a bench or conducting in-person experiments might have, the Simmerling group could work every day, forging ahead to understand the way the protein operates and to look for critical steps or weaknesses that might assist doctors down the road.

Recently, Simmerling and his lab group exchanged emails over Thanksgiving, during which the group felt this commitment to COVID research gave them a “shared purpose” and helped them feel as if they were “doing something.”

While the Simmerling lab appreciated the opportunity to contribute to efforts to combat COVID-19, they also recently received a national award in high-performance computing. Called the Gordon Bell Special Prize, the award recognizes “outstanding research achievement towards the understanding of the COVID-19 pandemic through the use of high-performance computing.”

The award, which was announced at the virtual SuperComputing 2020 Conference and recognizes the work of the Simmerling lab and some collaborators they worked with since early in the pandemic, includes a $10,000 prize.

The kind of research Simmerling and his team conducted may help either with this specific virus or with any others that might threaten human health again.

“We were not well prepared in science and humanity in general,” Simmerling said. “We have to come up with better tools.”

While he is pleased that pharmaceutical companies are getting closer to introducing vaccines for COVID-19, Simmerling said any such solutions would apply to this specific virus and not to any subsequent forms of coronavirus or other potential threats to human health.

People who contracted SARS or MERS, which are coronavirus cousins, didn’t develop an immunity to COVID-19.

“Even if we all get vaccinated, that won’t help us for the next one, and we’ll likely have other ones,” Simmerling explained. “Science needs to do a better job getting deeper into how these work.”

At this point, the models Simmerling and his staff have created are working and are providing the kind of clues that could contribute to providing suggestions for future experiments. The lab is “now at the stage where we are seeing new things not seen in the experiments and suggesting new experiments to test our hypotheses,” said Simmerling.

His lab has focused on the dynamics of proteins and other biomolecules to see how they move around in time. He simulates the shape changes when molecules interact, including in the 2000s when he worked on proteins in the human immunodeficiency virus.

Simmerling likens the study to the process of shaking other people’s hands. When two people come together, their hands adapt to each other when they interact, changing shape as they move up and down.

With the spike protein in COVID-19, scientists have seen what it looks like before it interacts. The structure after it unlocks the cell is fuzzier and scientists aren’t sure if they are relevant to the actual virus or something vaguely similar to it.

“We only get snapshots at the beginning and the end,” he said. “What we need to do is figure out how it works.”

He uses software his lab has developed with a few other labs in the country. Scientists around the world use this Amber system. They take steps in time and calculate the forces on the atom, which requires millions of iterations.

Simmerling said other people sometimes think he and his team download the structure, plug it into a computer, run it and then publish a paper. That’s far from the case, as the computer does the number crunching, but people like Simmerling spend considerable time trying to understand a molecule like the spike protein well enough to develop ideas about how it might move and change.

Simmerling took a circuitous route to the world of using chemistry and physics on a computer. When he entered college at the University of Illinois at Chicago, he wanted to be a chemist. The only problem was that he didn’t enjoy working in the lab with all the chemicals.

Half way through his college education, he left school and started working at a computer company. Eight years later, he decided to return to college, where he planned to earn his chemistry degree.

“When I went back to school, I told my [teaching assistant] that I wish I could do [chemistry] on computers rather than experiments,” Simmerling said. “He introduced me to the professor [Ron Elber] who became my PhD advisor. That brought together things I was interested in.”

He knew programming and how to use computers.

“Sometimes, you’re the sum of your choices,” Simmerling said.

He and his wife Maria Nagan, who also does computer modeling at Stony Brook University, live in Port Jefferson. In non-pandemic times, Simmerling enjoys sailing throughout the year.

As for the prize, Simmerling said the “recognition is nice” and he would like his lab to contribute to “models to change how we combat infectious disease.”