The limits of bio-molecular modeling with large language models : a cross-scale evaluation

Large Language Models (LLMs) have demonstrated historic breakthroughs in general reasoning with early successes in biomedical science. However, existing LLM benchmarking emphasizes factual recall, offering limited insight into model performance on frontier and multimodal tasks. We assembled BioEVAL (BioEngineering Validation of AI and LLMs), a global, multi-institutional initiative designed to assess experimental reasoning capability across bioengineering (BE) subfields. BioEVAL spans 11 major BE subfields plus a set of uncategorized items, bringing together 22 research groups to create a PhD-level benchmark comprising 608 evaluation items: 1) 380 multiple-choice questions (MCQs, 359 retained after audit), 2) 218 literature synthesis tasks, and 3) 10 multimodal problems with experimental image interpretation. Benchmark items underwent authoring-group expert review and centralized quality control before evaluation. Following evaluation, a blinded cross-group consensus audit of the highest- and lowest-accuracy MCQ items flagged 21 questions for revision or removal; these were withheld, and all reported MCQ results are computed on the 359 retained items. We evaluated diverse cloud-scale foundation/multimodal models (e.g., ChatGPT, Gemini, and Grok) and locally deployable models suitable for inference on consumer-grade GPUs. Models achieved the highest accuracy of up to 90% on MCQs, similarity score of 0.72 on literature synthesis, and accuracy of 80% on a small sample of multimodal reasoning questions, with substantial performance variation across subfields. Leaderboard rankings characterize current capabilities, limitations, and development priorities across the evaluated BE task categories. BioEVAL is maintained as an extensible benchmark with standardized protocols for continuing expert item contribution and model evaluation.

Large Language Models (LLMs) have the potential to accelerate small molecule drug design due to their ability to reason about information from diverse sources and formats. However, their practical utility remains unclear due to the lack of benchmarks that reflect real-world scenarios. In this work, we introduce a suite of chemically-grounded tasks spanning molecular property prediction, molecular representation transformations, and molecular design. Importantly, we formulate these tasks as reinforcement learning (RL) environments, enabling a unified approach for evaluation and post-training. Across three model families, we find that frontier models are increasingly proficient at chemical tasks, but that there is significant room for improvement, especially in experimental settings with low data. Critically, we show that RL-based post-training can substantially improve performance. A smaller model post-trained on our environments becomes competitive with state-of-the-art frontier models, despite a significantly weaker base model. This suggests a practical route toward employing LLMs in drug discovery; by combining carefully-designed evaluation tasks with targeted post-training, we can both elucidate and close critical capability gaps.

Large language models (LLMs) are increasingly employed to predict molecular properties. However, prediction error alone cannot distinguish prediction from retrieval of published values. We audit 22 frontier models on 12 molecular regression datasets in a zero-shot setting, assessed against a molecule-blind reference derived from each dataset's labels. Significant retrieval is concentrated on 5 datasets, with isolated flagged LLMs elsewhere. Increasing the reasoning setting raises the number of flagged model--dataset combinations from 47 to 89 of 264. An in-context blinding experiment reduces retrieval but leaves a quarter of the combinations flagged. Blinding changes model rankings and increases errors. Because blinding also removes chemically interpretable structure, the error increase can only be partially attributed to reduced retrieval.