When reading the novel Jurassic Park as a teenager, Jerry Parks found the passages about gene sequencing and supercomputers fascinating, but never imagined he might someday pursue such futuristic-sounding science. Fast-forward to today when Parks has achieved a broad range of real-life discoveries based on an understanding of the molecular processes that underpin everything from toxic methylmercury formation to viral infection in humans.

As lead for the Molecular Biophysics group at the Department of Energy’s Oak Ridge National Laboratory, Parks uses his expertise in computational chemistry and bioinformatics to unlock the inner workings of proteins, molecules that govern cellular structure and function and are essential to life.

Applying his expertise across science domains was one of the reasons he chose the versatile research environment at ORNL. “Large multidisciplinary projects are a nice way to get a lot of diverse scientists into a room on the same project, all working toward a common goal,” Parks said.

His first experience at ORNL was as a postdoctoral researcher working on a team exploring the origins of how inorganic mercury transforms into the potent neurotoxin methylmercury.

“I hardly knew anything about mercury, but I quickly started to learn about the microbiology involved, the genetics and genomics, the lab-based work, and even a bit of the field work,” Parks said. “I knew I needed to communicate without jargon about my research in a way that was understandable by people who did very different types of science.”

The result of that effort was the landmark discovery of the proteins responsible for bacterial mercury methylation. The scientists identified two genes, hgcA and hgcB, present in all known mercury-methylating bacteria and archaea and confirmed the work with genome editing. Parks was principal investigator for a follow-on project that created a 3D computational model of the protein complex to support additional research into mercury methylation.

A unifying theme across science domains

It was a quite different project that took Parks into the realm of antiviral drug discovery. Spurred by the COVID-19 pandemic, he led a multi-institutional team that designed a molecule to disrupt the infection mechanism of the SARS-CoV-2 coronavirus.

The molecule targeted a less-studied enzyme, PLpro, that helps the virus multiply and interferes with the host body’s immune response. Parks and colleagues used computational modeling to predict whether their designs would bind to and disrupt the enzyme. The team designed molecules to covalently bind PLpro by forming a strong chemical bond, in contrast to most drugs that bind noncovalently. They then synthesized the molecules and tested them to confirm their predictions.

“The drug discovery process can take many years and is very expensive. We wanted to kickstart the process by developing a new class of inhibitor that targets the virus in a different way from other drugs, and could potentially be used on new variants or a new type of coronavirus,” Parks said. “It’s good to have multiple weapons in your arsenal against viruses.”

Parks is also on a team of ORNL scientists designing enzymes to efficiently break down polymers in plastic waste. He’s making computational models of enzymes that have been identified as candidates for enhancement because of their natural ability to degrade nylon.

“So many important phenomena happen at the scale of proteins,” Parks said. “In this enzyme engineering project, for instance, we first need to know how these enzymes work and how they recognize nylon and break it down. Understanding the processes at the molecular level can help us design new approaches to deal with nylon pollution.

“Through most of my research,  there’s the unifying theme of protein structure, function, mechanism and inhibition. The topics are different, but the techniques are often very similar, and I like being able to apply these methods to different fields.”

Communicating across disciplines is vital to the research, and something Parks said he’s worked to maintain and improve as he has taken on a panoply of projects. “I love to talk about science and communicate and learn what other people are doing at the lab. That’s how I can contribute, when I start understanding what everyone else is working on and how my skills can fit in and help out,” he said.