Systematic Exploration of Small-Molecule Binding via a Large Language Model Trained on Textualized Protein-Ligand...

Emergent Large Language Models (LLMs) show impressive capabilities in performing a wide range of tasks. These models can be harnessed for biophysical use as well. The main challenge in this endeavor lies in transforming 3D chemical data into 1D language-like data. We developed a method to transform molecular data into language-like data and tokenize it for LLM use in a biophysical context. We then trained a model and validated it with a known protein-ligand complex. Using the pre-trained result, the model can assess the chemical properties of targets, detect shared binding properties and structures, and reveal related drugs. The model and the synthetic language to describe binding interactions uncovered novel protein-protein networks influenced by ligands, indicating functionally related yet previously unreported interactions.