MolRGen: A Training and Evaluation Setting for De Novo Molecular Generation with Reasonning Models
On the map: LLM reasoning → Clinical and biomedical applications
Abstract (arXiv)
Recent reasoning-based large language models have shown strong performance on tasks with verifiable outcomes, but their use in de novo molecular generation remains limited by the lack of training environments where rewards can be computed without reference molecules. We introduce MolRGen, a benchmark and molecular verifier for training and evaluating reasoning LLMs on de novo molecular generation. MolRGen contains approximately 4,500 protein-pocket targets, resulting in 50k multi-objective optimization prompts combining docking scores with molecular properties such as QED, synthetic accessibility, logP, and physicochemical descriptors. Unlike caption-based generation or molecule-editing benchmarks, MolRGen evaluates molecules proposed from scratch by computing rewards at generation time. We benchmark general-purpose and chemistry-specialized open-source LLMs and introduce a diversity-aware top-k metric to measure whether models can generate a diverse set of high-scoring molecules. Finally, we use the verifier to fine-tune a 128B LLM with GRPO, showing improved performance, at the cost of a diversity-exploitation trade-off. MolRGen provides a scalable testbed for studying verifier-based reasoning and reinforcement learning in molecular design.
Key facts. No citing papers in the map yet (data through 7 Oct 2026). Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning. Builds on 27 of its 46 references that are in the map. First posted on arXiv 18 Mar 2026.
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27 of 46 references.
Closest ancestors · 4
Same direction, newest first
- 2025Reasoning-Enhanced Large Language Models for Molecular Property Prediction11 Oct
- 2025Mol-R1: Towards Explicit Long-CoT Reasoning in Molecule Discovery11 Aug
- 2025Training a Scientific Reasoning Model for Chemistry4 Jun
- 2025BioReason: Incentivizing Multimodal Biological Reasoning within a DNA-LLM Model29 May
Other references · 23
- 2024The Llama 3 Herd of Modelscited by 14,192
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- 2025Qwen3 Technical Reportcited by 8,195
- 2025DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learningcited by 6,146
- 2025gpt-oss-120b & gpt-oss-20b Model Cardcited by 1,258
- 2025Does Reinforcement Learning Really Incentivize Reasoning Capacity in LLMs Beyond the Base Model?cited by 948
- 2017Ray: A Distributed Framework for Emerging AI Applicationscited by 516
- 2025MiniMax-M1: Scaling Test-Time Compute Efficiently with Lightning Attentioncited by 248
- 2023Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Modelscited by 131
- 2024LlaSMol: Advancing Large Language Models for Chemistry with a Large-Scale, Comprehensive, High-Quality Instruction Tuning Datasetcited by 124
- 2024Towards 3D Molecule-Text Interpretation in Language Modelscited by 65
- 2025Magistralcited by 57
11 more
- 2024RGFN: Synthesizable Molecular Generation Using GFlowNetscited by 39
- 2024Are large language models superhuman chemists?cited by 34
- 2023Genetic algorithms are strong baselines for molecule generationcited by 31
- 2024Text-Guided Molecule Generation with Diffusion Language Modelcited by 31
- 2024Generative Artificial Intelligence for Navigating Synthesizable Chemical Spacecited by 18
- 2025GeLLMO: Generalizing Large Language Models for Multi-property Molecule Optimizationcited by 16
- 2025Mol-LLaMA: Towards General Understanding of Molecules in Large Molecular Language Modelcited by 16
- 2025Exploring Synthesizable Chemical Space with Iterative Pathway Refinementscited by 7
- 2025Guiding Diffusion Models with Reinforcement Learning for Stable Molecule Generationcited by 4
- 2023Molecular De Novo Design through Transformer-based Reinforcement Learningcited by 3
- 2024SIU: A Million-Scale Structural Small Molecule-Protein Interaction Dataset for Unbiased Bioactivity Predictioncited by 2
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- 2025BioMedGPT-Mol: Multi-task Learning for Molecular Understanding and Generation
- 2025NovoMolGen: Rethinking Molecular Language Model Pretraining
- 2024Crossing New Frontiers: Knowledge-Augmented Large Language Model Prompting for Zero-Shot Text-Based De Novo Molecule Design
- 2026M^4olGen: Multi-Agent, Multi-Stage Molecular Generation under Precise Multi-Property Constraints
- 2023Domain-Agnostic Molecular Generation with Chemical Feedback
- 2026Mol-Debate: Multi-Agent Debate Improves Structural Reasoning in Molecular Design
- 2025MT-Mol:Multi Agent System with Tool-based Reasoning for Molecular Optimization