Steffen Lindert, assistant professor in the Department of Chemistry and Biochemistry and faculty member under the university’s Translational Data Analytics Discovery Theme, has received a five-year, $1.8 million R01 grant from the National Heart, Lung and Blood Institute to study heart muscle contraction and identify potential new drugs to treat heart failure.  

Lindert and his team will use computer-aided drug discovery to pinpoint new therapeutics for left ventricular systolic dysfunction, one of the most common types of heart failure in which the heart loses some of its ability to contract and can’t pump with enough force.

Current pharmaceuticals for this type of heart failure have severe side effects, but medications known as calcium sensitizers may be a promising alternative.  

“With every beat of your heart, calcium gets released,” Lindert said. “If you’re young and healthy, then a certain concentration of calcium yields a certain contractility effect. If you have heart failure, that same concentration doesn’t give that same effect.”

Calcium sensitizers can make the heart more receptive to calcium, therefore improving heart function without as many side effects. These drugs are still in the early stages of development, and none have been approved in the U.S., Lindert said.

His team is specifically looking at a protein called troponin C, which plays an integral role in cardiac muscle contraction and calcium signaling. Lindert is developing new computational methods to better understand troponin’s role in contraction.

Drug compounds that can adjust calcium sensitivity within this specific protein will be identified using advanced techniques and resources at the Ohio Supercomputer Center.

To do this will require some innovation, as computer simulations involving these complex molecular processes are currently oversimplified. Lindert’s team hopes to create new computational models that can better test the accuracy and efficacy of these drugs.  

The compounds with the best predicted results will then be tested in the lab of Dr. Jonathan Davis, associate professor of physiology and cell biology at the College of Medicine.

“The field has come pretty far,” Lindert said. “20 or 30 years ago, you couldn’t use computers for drug discovery.”