Automating RNA-Ligand Interaction Modeling via a Self-Improving LLM Agent

Abstract

Precise modeling of RNA-ligand interactions is essential for understanding RNA functionality and designing RNA-targeted therapeutics. Current computational approaches largely focus on predicting discrete binding sites, limiting their applicability to complex RNA regions that may harbor multiple or diffuse ligand binding motifs. Here, we present RLAgent, an interactive agent framework designed to predict ligand interactions at the RNA region level, enabling higher-resolution and more flexible modeling than conventional site-centric approaches. RLAgent reframes the RNA-ligand prediction workflow as a dialogue-driven process. Through a natural language interface, users can interactively configure modeling preferences without writing code. A locally hosted large language model (LLM) acts as the core orchestration agent, automating all key components of the modeling pipeline, including data validation, feature encoding, model training, evaluation, and visualization. This agent-based design lowers technical barriers and enhances reproducibility, making RNA-ligand prediction more accessible for both computational and experimental researchers.