Investigating the Ribosomal‐RNA: Protein Interactions and AI‐Assisted Discovery of Novel Inhibitors

Abstract This study explores novel ligands that potentially offer superior binding and stability compared to the peptidic molecules currently associated with the ribosomal RNA–protein complex. This study aims to elucidate the molecular mechanisms underlying protein–RNA interactions and their disruptions, identify potential therapeutic targets, and explore novel compounds capable of modulating these interactions for therapeutic benefit. We conducted molecular docking and dynamics simulations using advanced computational tools such as rDock and REINVENT4 to generate novel compounds. ADMET analysis confirmed the chosen compound's advantageous pharmacokinetic attributes and safety profiles. Among the generated compounds, C21, C23, C56, C120, and C195 were identified as the best candidate molecules for inhibiting protein–RNA interactions. These ligands demonstrated superior binding affinity and stability, outperforming the peptidic molecules bound to the reference protein–RNA–peptide complex structure.The ligand molecules were notable for their ability to settle into low–energy states, indicating a strong potential to outperform the peptide bound in the reference protein–RNA–peptide complex structure. These findings highlight the capability of these ligands to serve as more effective therapeutic agents and as superior alternatives to the current peptidic molecules, with implications for developing novel therapeutic strategies targeting protein–RNA interactions.