This award, under the Molecular Foundations for Biotechnology (MFB) program in the Division of Chemistry, funds Drs. Scott Aoki and Jonah Vilseck from the Indiana University School of Medicine to develop a computational strategy to accurately predict how unmodified and modified RNAs interact with proteins that control or regulate important biological functions. Chemical modifications to the bases in RNA affect their recognition by proteins and, consequently their function. With over 170 modifications identified thus far, new methods are required to elucidate how combinations of unmodified and modified RNAs interact with regulatory RNA-binding proteins. This project adapts a physics-based molecular modeling technique called λ-dynamics that, when paired with classic RNA biochemistry, determines the RNA sequence preferences of a host of RNA-binding proteins involved in gene expression. The research provides new insights into the biological function of RNA modifications in areas that impact biotechnology. In parallel, a summer program is being created that engages junior trainees in scientific literature about RNA modifications as an entrée into STEM careers. Current methods to study RNA-protein interactions are accurate but often expensive, time-consuming, and limited by available reagents. New methods are required to study how RNA and its modifications affect RNA-protein interactions and their subsequent roles in biology. λ-dynamics is an efficient computational method for