AI and the World's Hard Problems · Medicine & drug discovery · arXiv · 2026-10-26
What Transfers Across Protein Pockets? Experience Reuse in Molecular Optimization for Agentic Structure-Based Drug Design
LLM agents optimize ligands in protein pockets by editing step by step and docking each edit, and the probes they run could be kept in a shared experience base. The authors analyzed one run's full log over CrossDocked2020 test-set pockets and found that the separation of improving from worsening edits was largely explained by how much an edit changed molecular size, the action, and the round, not the target, though naming the target separated them several times more sharply. For unseen pockets, the transferable signals mainly described the edit and the resulting molecule, suggesting the base is more useful for prioritizing the agent's own docking proposals than for prescribing what to build.