M$^{4}$olGen: Multi-Agent, Multi-Stage Molecular Generation under Precise Multi-Property Constraints

Yizhan Li, Florence Cloutier, Sifan Wu, Ali Parviz, Boris Knyazev, Yan Zhang, Glen Berseth, Bang Liu

Keywords: LLM, Multi-agent System, Molecule Generation

TL;DR: We introduce a multi-Agent, multi-stage molecular generation under precise multi-property constraints along with the corresponding reasoning dataset.

Abstract: Generating molecules that satisfy precise numeric constraints over multiple physicochemical properties is critical and challenging. Although large language models (LLMs) are expressive, they struggle with precise multi-objective control and numeric reasoning without external structure and feedback. We introduce M$^{4}$olGen, a fragment-level, retrieval-augmented, two-stage framework for molecule generation under multi-property constraints. Stage I: Prototype generation: a multi-agent reasoner performs retrieval-anchored, fragment-level edits to produce a candidate near the feasible region. Stage II: RL-based fine-grained optimization: a fragment-level optimizer trained with Group Relative Policy Optimization (GRPO) applies one- or multi-hop refinements to explicitly minimize the property errors toward our target while regulating edit complexity and deviation from the prototype. A large, automatically curated dataset with reasoning chain of fragment edits and measured property deltas underpins both stages, enabling deterministic, reproducible supervision and controllable multi-hop reasoning. Unlike prior work, our framework better reasons about molecules by leveraging fragments and supports controllable refinement toward numeric targets. Experiments on generation under three property constraints (QED, LogP, and molecular weight) show consistent gains in validity and precise satisfaction of multi-property targets, outperforming strong LLMs and graph-based algorithms.

Primary Area: applications to physical sciences (physics, chemistry, biology, etc.)

Submission Number: 15437