Drug Discovery Center Integrates AI For Big Impact

A UNC Eshelman School of Pharmacy lab uses artificial intelligence to discover unique compounds and shares the software.

The UNC Eshelman School of Pharmacy is home to a scientific force driving the future of translational medicine — the Center for Integrative Chemical Biology and Drug Discovery. This center seamlessly blends chemistry, biology and computational science to discover new therapeutic agents and targets.

The center takes a fully integrated approach to drug discovery by bringing together all the expertise and infrastructure needed under one roof. Hits generated through artificial intelligence can be quickly tested and refined through the center’s collaborative groups. The groups are led by pharmacy school faculty:

• Lead discovery, center director and professor Ken Pearce
• Medicinal chemistry, professor Xiaodong Wang
• Chemical biology, associate professor Lindsey James
• Computational biophysics, associate professor Konstantin Popov

AI for drug discovery
Within the center, Popov is pioneering ways to integrate AI into drug discovery. His biophysics and informatics for drug discovery lab is using AI to tackle some of the world’s most pressing health challenges, including tuberculosis and cancer.

Popov and his team were invited to join Jeff Aubé, Eshelman Distinguished Professor, and Dr. Carl Nathan at Weill Cornell Medicine, the TB Alliance and the Gates Foundation on a large collaborative project that was winding down.

Using a novel AI-guided generative method, Popov’s team uncovered compounds capable of targeting a critical TB protein in just six months — with a fraction of the effort and time typically required.

“We were able to come up with several very promising compounds and in collaboration with chemists from Aubé’s group, boosted their enzyme potency more than 200-fold in just a few iterations,” said Popov. “But because of the flexibility of our approach, designed to work efficiently within a small, dynamic academic team, we were able to move much faster. “

For developing targeted cancer therapies, his group applied a similar strategy — using preliminary screens, conducted in the center, to identify promising molecules, then refining them with AI to design compounds that are more effective and less toxic to healthy cells.

Popov emphasizes that while AI is a powerful tool, it can’t succeed in isolation. “You need to incorporate reality checks along the way,” he said. “Otherwise, the model can hallucinate and generate compounds that look great on the screen but can’t actually be synthesized or would be too toxic. By working closely with chemists, we keep AI grounded in biological reality.”

This balance of computational innovation and experimental collaboration has enabled his lab to design biologically relevant and synthetically feasible de novo compounds — molecules that don’t exist in any catalog. This approach allows the creation of entirely new chemical starting points that would be impossible with traditional drug screening, which is limited to testing compounds that already exist in libraries.

The DELi Platform
Popov is also committed to democratizing access to AI. His lab recently developed the DNA-Encoded Library informatics platform, the first open-source software capable of rivaling commercial tools for analyzing DNA-encoded library data.

“Very few published AI tools developed for research are actually used,” said Popov. “We want to change that by building practical tools that are easy to access and use in academia.”

Unlike proprietary software controlled by large companies, DELi is freely available, easy to install and provides extensive documentation and ongoing support from Popov’s team. “It’s the first open-source package of its kind, and the feedback has been amazing,” Popov said.

He hopes to spark broader adoption of AI tools across the academic community, helping labs everywhere accelerate discovery without prohibitive costs.

“AI can accelerate the early stages of drug discovery dramatically,” Popov said. “But it only works in the right hands — when scientists bring their knowledge of chemistry and biology to guide the process. That’s what makes the difference.”