September 2023
Ilyas Yildirim, Ph.D., an Assistant Professor in the Department of Chemistry and Biochemistry at the Charles Schmidt College of Science, co-authored a recently featured article in the prestigious Nucleic Acids Research journal. The high-profile, peer-reviewed journal, published by Oxford University Press, highlighted his team’s research on the “Conformational dynamics of RNA G4C2 and G2C4 repeat expansions causing ALS/FTD using NMR and molecular dynamics studies.”
“Targeting RNA structures with small molecules is a novel therapeutic approach, which can rescue various disease-associated phenotypes,” explained Yildirim. “RNA loops are dynamic, which makes them good targets in drug design. Capitalization of specific RNA conformations with small molecules could provide a novel approach in RNA therapeutics for currently incurable diseases.”
The researchers studied the conformational dynamics adopted by 2×2 GG/GG and 2×2 CC/CC RNA loops, using both experimental and computational methods and characterized the structure and underlying dynamics. For the first time, the team showed that RNA 2×2 GG/GG loops prefer syn-anti/anti-syn and anti-syn/anti-syn conformations.
“Such a structural change in RNA G4C2 due to interaction with a small molecule is observed for the first time,” stated Yildirim. “This observation provides a new direction in targeting RNA G4C2 repeats with small molecules that can inhibit the pathobiological effects driven by this expanded repeat.”
