# A Survey of Large Language Models for Text-Guided Molecular Discovery: from Molecule Generation to Optimization

arXiv: https://arxiv.org/abs/2505.16094 · HTML: https://mlsanity.com/paper/2505.16094/

## Key facts

- Cited by 13 papers in the map (data through 14 Oct 2026).
- Builds on 59 of its 130 references that are in the map.
- First posted on arXiv 22 May 2025.

## Builds on (most cited first, 30 of 59)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [SQuAD: 100,000+ Questions for Machine Comprehension of Text](https://mlsanity.com/paper/1606.05250/) (2016)
- [Open Graph Benchmark: Datasets for Machine Learning on Graphs](https://mlsanity.com/paper/2005.00687/) (2020)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [MolGAN: An implicit generative model for small molecular graphs](https://mlsanity.com/paper/1805.11973/) (2018)
- [ReTool: Reinforcement Learning for Strategic Tool Use in LLMs](https://mlsanity.com/paper/2504.11536/) (2025)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models](https://mlsanity.com/paper/1811.12823/) (2018)
- [Therapeutics Data Commons: Machine Learning Datasets and Tasks for Drug Discovery and Development](https://mlsanity.com/paper/2102.09548/) (2021)
- [Fr'echet ChemNet Distance: A metric for generative models for molecules in drug discovery](https://mlsanity.com/paper/1803.09518/) (2018)
- [Reasoning Models Can Be Effective Without Thinking](https://mlsanity.com/paper/2504.09858/) (2025)
- [MoFlow: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/2006.10137/) (2020)
- [Multi-modal Molecule Structure-text Model for Text-based Retrieval and Editing](https://mlsanity.com/paper/2212.10789/) (2022)
- [LlaSMol: Advancing Large Language Models for Chemistry with a Large-Scale, Comprehensive, High-Quality Instruction Tuning Dataset](https://mlsanity.com/paper/2402.09391/) (2024)
- [A Review of Large Language Models and Autonomous Agents in Chemistry](https://mlsanity.com/paper/2407.01603/) (2024)
- [A Comprehensive Survey of Scientific Large Language Models and Their Applications in Scientific Discovery](https://mlsanity.com/paper/2406.10833/) (2024)
- [Empowering Molecule Discovery for Molecule-Caption Translation with Large Language Models: A ChatGPT Perspective](https://mlsanity.com/paper/2306.06615/) (2023)
- [MOOSE-Chem: Large Language Models for Rediscovering Unseen Chemistry Scientific Hypotheses](https://mlsanity.com/paper/2410.07076/) (2024)
- [The Synthesizability of Molecules Proposed by Generative Models](https://mlsanity.com/paper/2002.07007/) (2020)
- [DrugAssist: A Large Language Model for Molecule Optimization](https://mlsanity.com/paper/2401.10334/) (2023)
- [ChemReasoner: Heuristic Search over a Large Language Model's Knowledge Space using Quantum-Chemical Feedback](https://mlsanity.com/paper/2402.10980/) (2024)
- [A Survey of Generative AI for de novo Drug Design: New Frontiers in Molecule and Protein Generation](https://mlsanity.com/paper/2402.08703/) (2024)
- [Multimodal Large Language Models for Inverse Molecular Design with Retrosynthetic Planning](https://mlsanity.com/paper/2410.04223/) (2024)

## Built on by (most cited first, 13 of 13)

- [Rethinking Entropy Interventions in RLVR: An Entropy Change Perspective](https://mlsanity.com/paper/2510.10150/) (2025)
- [A Systematic Survey on Large Language Models for Evolutionary Optimization: From Modeling to Solving](https://mlsanity.com/paper/2509.08269/) (2025)
- [MolMem: Memory-Augmented Agentic Reinforcement Learning for Sample-Efficient Molecular Optimization](https://mlsanity.com/paper/2604.12237/) (2026)
- [CoAct: Co-Active LLM Preference Learning with Human-AI Synergy](https://mlsanity.com/paper/2604.17501/) (2026)
- [Round-trip Reinforcement Learning: Self-Consistent Training for Better Chemical LLMs](https://mlsanity.com/paper/2510.01527/) (2025)
- [GlassMol: Interpretable Molecular Property Prediction with Concept Bottleneck Models](https://mlsanity.com/paper/2603.01274/) (2026)
- [Closed-Loop Molecular Inverse Design with Semantic LLM Surrogates](https://mlsanity.com/paper/2608.22967/) (2026)
- [Assay2Mol: large language model-based drug design using BioAssay context](https://mlsanity.com/paper/2507.12574/) (2025)
- [ES-Merging: Biological MLLM Merging via Embedding Space Signals](https://mlsanity.com/paper/2603.14405/) (2026)
- [ReContraster: Making Your Posters Stand Out with Regional Contrast](https://mlsanity.com/paper/2604.10442/) (2026)
- [HopRank: Self-Supervised LLM Preference-Tuning on Graphs for Few-Shot Node Classification](https://mlsanity.com/paper/2604.17271/) (2026)
- [M3OS: A Monte Carlo Graph Search-Orchestrated Multi-Agent LLM System for Evidence-Traced Molecular Optimization](https://mlsanity.com/paper/2609.34491/) (2026)
- [Autonomous Science Bench: Evaluating AI Agents for Autonomous Scientific Discovery](https://mlsanity.com/paper/2610.18449/) (2026)

## Abstract (arXiv)

Large language models (LLMs) are introducing a paradigm shift in molecular discovery by enabling text-guided interaction with chemical spaces through natural language, symbolic notations, with emerging extensions to incorporate multi-modal inputs. To advance the new field of LLM for molecular discovery, this survey provides an up-to-date and forward-looking review of the emerging use of LLMs for two central tasks: molecule generation and molecule optimization. Based on our proposed taxonomy for both problems, we analyze representative techniques in each category, highlighting how LLM capabilities are leveraged across different learning settings. In addition, we include the commonly used datasets and evaluation protocols. We conclude by discussing key challenges and future directions, positioning this survey as a resource for researchers working at the intersection of LLMs and molecular science. A continuously updated reading list is available at https://github.com/REAL-Lab-NU/Awesome-LLM-Centric-Molecular-Discovery.