Quantum Mechanics Helps Uncover Atypical Recognition Features in the Flavin Mononucleotide Riboswitch.

Estimating the binding energies of small molecules to RNA could help uncover their molecular recognition characteristics and be used to rationally design RNA-targeting chemical probes. Here, we leveraged the ability of the fragment molecular orbital (FMO) method to provide detailed pairwise energetic information to examine the interactions between the aptamer domain of the flavin mononucleotide (FMN)-responsive riboswitch and small-molecule ligands. After developing an efficient protocol for executing high-level FMO calculations on RNA-ligand complexes, we applied our protocol to nine FMN-aptamer-ligand complexes.