The paper explores how large language models (LLMs) can be trained for small-molecule drug design by using synthetic tasks that are cheaper to evaluate. By employing a curriculum that gradually increases task difficulty, the authors demonstrate that LLMs can learn design strategies that outperform larger models on structure-based lead optimization. This approach shows that scaling post‑training with synthetic tasks can effectively adapt LLMs to high‑cost experimental scenarios that are otherwise infeasible to train on directly.
By Frank Hu, Shriram Chennakesavalu, Zichen Wang, Patricia Suriana, Bodhi Vani, Kirill Shmilovich, Kangway Chuang, Colin Grambow
Monroe is a new molecular foundation model that improves upon existing models by pre‑training on over 81 million molecules from the PM6 quantum chemistry dataset, enhancing stereochemistry representation, and introducing novel training losses such as conformer denoising and embedding decorrelation. It also incorporates a prior‑data‑fitted model (TabPFN) for downstream in‑context prediction and demonstrates superior performance on Polaris benchmarks and activity cliff tests. Ablation studies show that the PFN‑based downstream approach can upgrade other models, producing state‑of‑the‑art variants MiniMol_PFN and CheMeleon_PFN.
By Blazej Banaszewski, Andrew W. Fitzgibbon
The paper introduces a multitask large reasoning model for molecular science that incorporates chemical knowledge via a multispecialist architecture, chain-of-thought supervision, and molecule-informed reinforcement learning. It coordinates prediction and inference specialists across ten molecular tasks—including description, generation, nomenclature translation, property prediction, and reaction prediction—using task-conditioned routing. The model surpasses more than 20 general-purpose and molecular large language models, improving aggregate performance by 50.3% and outperforming leading multitask baselines on most tasks, while maintaining interpretable chemical inference and demonstrating a workflow for CNS candidate generation and retrosynthetic planning.
By Pengfei Liu, Shuang Ge, Xiaobo Wang, Xin Liu, Jun Tao, Yan Li, Chao Liu, Ling Chen, Zhixiang Ren
arXiv:2507.07426v4 Announce Type: replace
Abstract: Recent advances in large language models have demonstrated considerable potential in scientific domains such as drug repositioning. However, their...
By Zerui Yang, Yuwei Wan, Siyu Yan, Yudai Matsuda, Tong Xie, Linqi Song
arXiv:2604. 26498v3 Announce Type: replace Abstract: The rapid growth of molecular foundation models and large language models (LLMs) has encouraged a scale centred view of AI in drug discovery, in which larger pretrained models are expected to supersede compact cheminformatics models.
By Jinjiang Guo, Sheng Ding
The paper reports a large-scale, compute-controlled study of Chemical Language Models (CLMs) involving over 30,000 experiments across different molecular representations, tokenizations, model sizes, datasets, and architectures. It finds clear scaling trends in pretraining loss but shows that these improvements do not translate into proportional gains in goal-directed molecular design, with chemical syntax saturating early while semantic properties develop more slowly. The authors release a new suite of models, NovoMolGen, that achieves state-of-the-art results in drug discovery tasks, highlighting a disconnect between representation learning and downstream design and calling for new pretraining paradigms that target chemical semantics.
By Roshan Balaji, Kamran Chitsaz, Quentin Fournier, Nirav Pravinbhai Bhatt, Sarath Chandar
arXiv:2607. 19044v1 Announce Type: new Abstract: Leveraging large language models (LLMs) for molecular generation has shown remarkable potential in chemical and drug design.
By Mingxuan Ouyang, Hao Lan, Wanyu Lin
The paper introduces MolPAIR, a framework that enhances tabular foundation models (TFMs) for predicting molecular properties under structural shifts by incorporating molecule-level and molecular-pair contexts without task‑specific parameter updates. MolPAIR refines initial predictions from a global TFM by using a second frozen TFM to predict differences in prediction errors between a query molecule and labeled reference molecules. Experiments on 58 MoleculeACE and Polaris tasks show that MolPAIR improves performance on 46 tasks across multiple molecular representations and TFM backbones, demonstrating that explicit molecular comparisons strengthen tabular in‑context learning for structural generalization.
By Jinmo Lee, Dooho Lee, Minho Jeong, Jaemin Yoo
The study evaluates four pretrained molecular language models on six virtual libraries covering drug discovery, organic materials, and catalysis. It finds that native embeddings vary widely in performance, while molecular fingerprints remain consistently strong. Fine‑tuning the models on library‑specific data markedly improves sample efficiency, with several adapted encoders outperforming others across all tasks.
By Henrik Wille, Luis-Finley Sch\"utz, Felix Strieth-Kalthoff
arXiv:2601.00581v3 Announce Type: replace-cross
Abstract: We introduce AceFF, a pre-trained machine learning interatomic potential (MLIP) optimized for small molecule drug discovery. While MLIPs have...
By Stephen E. Farr, Stefan Doerr, Antonio Mirarchi, Alireza Moradzadeh, Francesc Sabanes Zariquiey, Saee Paliwal, Gianni De Fabritiis
BOOM is a new benchmark for evaluating out‑of‑distribution (OOD) molecular property predictions in machine learning. It provides chemically‑informed tests across common property prediction tasks and assesses over 150 model‑task combinations. The study shows that current models, including chemical foundation models, struggle to generalize OOD, with the best model still exhibiting three times higher error than in‑distribution predictions.
By Evan R. Antoniuk, Shehtab Zaman, Tal Ben-Nun, Peggy Li, James Diffenderfer, Busra Sahin, Obadiah Smolenski, Everett Grethel, Tim Hsu, Anna M. Hiszpanski, Kenneth Chiu, Bhavya Kailkhura, Brian Van Essen
arXiv:2610.19123v1 Announce Type: new
Abstract: Generating novel molecules with desired properties is a central challenge in drug discovery. Although foundational work focused on de novo generation,...
By Hannah Lawrence, Bodhi P. Vani, Ji Won Park, Natasa Tagasovska, Samuel Don Stanton, Andrew Martin Watkins, Michael Maser, Ewa M. Nowara