ToolMol: Evolutionary Agentic Framework for Multi-objective Drug Discovery

arXiv:2605.12784v1 Announce Type: new Abstract: Advances in large language models (LLMs) have recently opened new and promising avenues for small-molecule drug discovery. Yet existing LLM-based approaches for molecular generation often suffer from high rates of invalid and low-quality ligand candidates, a result of the syntactic limitations of current models with regard to molecular strings. In this paper, we introduce exttt{ToolMol}, an evolutionary agentic framework for de novo drug design. exttt{ToolMol} combines a multi-objective genetic algorithm with an agentic LLM operator that iteratively updates the ligand population. We build a comprehensive toolbox of RDKit-backed functions that allows our agentic operator to consisently make precise ligand modifications. exttt{ToolMol} achieves state-of-the-art performance on multi-objective property optimization tasks, discovering drug-like and synthesizable ligands that have >10% stronger predicted binding affinity compared to existing methods, evaluated on three protein targets. exttt{ToolMol} ligands additionally achieve state-of-the-art results in gold-standard Absolute Binding Free Energy scores, gaining over existing methods by over 35%. By studying chain-of-thought reasoning traces, we observe that tool-calling enables the model to more faithfully execute its planned modifications, efficiently exploiting the strong chemical prior knowledge in LLMs.

Source: arXiv cs.LG | 2026-05-14