Study combines data, molecular simulations to accelerate drug discovery

The study, published Aug. 30 in the journal Science Advances, offers renewed promise when it comes to discovering new drugs.

"The hope is we can speed up the timeline of drug discovery from years to months," said Alex Thorman, PhD, co-first author and a postdoctoral fellow in the Department of Environmental and Public Health Sciences in the College of Medicine.

Researchers combined two approaches for screening potential new drugs. First, they used a database from the Library of Integrated Network-based Cellular Signatures (LINCS) to screen tens of thousands of small molecules with potential therapeutic effects simultaneously. Then they combined the search with targeted docking simulations used to model the interaction between small molecules and their protein targets to find compounds of interest. That sped up the timing of the work from months to minutes -- taking weeks of work required for initial screening down to an afternoon.

Thorman said this faster screening method for compounds that could become drugs accelerates the drug research process. But it's not only speed that is crucial.

He added that this newer approach is more efficient at identifying potentially effective compounds.

"And the accuracy will only improve, hopefully offering new hope to many people who have diseases with no known cure, including those with cancer," Thorman said.

It can also create more targeted treatment options in precision medicine, an innovative approach to tailoring disease prevention and treatment that takes into account differences in people's genes, environments and lifestyles.

"An accelerated drug discovery process also could be a game changer in the ability to respond to public health crises, such as the COVID-19 pandemic," said Thorman. "The timeline for developing effective drugs could be expedited."

The other co-first authors were Jim Reigle, PhD, a postdoctoral fellow at Cincinnati Children's Hospital, and Somchai Chutipongtanate, PhD, an associate professor in the Department of Environmental and Public Health Sciences in the College of Medicine.

The corresponding authors of the study were Jarek Meller, PhD, a professor of biostatistics, health informatics and data sciences in the College of Medicine, and Andrew Herr, PhD, a professor of immunobiology in the Department of Pediatrics in the College of Medicine.

Other co-investigators included Mario Medvedovic, PhD, professor and director of the Center for Biostatistics and Bioinformatics Services in the College of Medicine, and David Hildeman, PhD, professor of immunobiology in the College of Medicine. Both Herr and Hildeman have faculty research labs at Cincinnati Children's Hospital.

This research was funded in part by grants from the National Institutes of Health, a Department of Veterans Affairs merit award, a UC Cancer Center Pilot Project Award and a Cincinnati Children's Hospital Innovation Fund award.

Those involved in the research are also co-inventors on three U.S. patents that are related to their work and have been filed by Cincinnati Children's Hospital.